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Inflammation and neuropeptides: the connection in diabetic wound healing

Published online by Cambridge University Press:  13 January 2009

Leena Pradhan ,
Christoph Nabzdyk ,
Nicholas D. Andersen ,
Frank W. LoGerfo  and
Aristidis Veves
Leena Pradhan
Affiliation:
Department of Surgery, Division of Vascular Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Christoph Nabzdyk
Affiliation:
Charité University Medicine, Joined Medical Faculty of Free University and Humboldt University, Berlin, Germany.
Nicholas D. Andersen
Affiliation:
Department of Surgery, Division of Vascular Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Frank W. LoGerfo
Affiliation:
Department of Surgery, Division of Vascular Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Aristidis Veves*
Affiliation:
Department of Surgery, Microcirculation Laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
*
*Corresponding author: Aristidis Veves, Microcirculation Laboratory, Beth Israel Deaconess Medical Center, Palmer 317, West Campus, One Deaconess Rd, Boston, MA 02215, USA. Tel: +1 617 632 7075; Fax: +1 617 632 0860; E-mail: aveves@bidmc.harvard.edu
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Abstract

Abnormal wound healing is a major complication of both type 1 and type 2 diabetes, with nonhealing foot ulcerations leading in the worst cases to lower-limb amputation. Wound healing requires the integration of complex cellular and molecular events in successive phases of inflammation, cell proliferation, cell migration, angiogenesis and re-epithelialisation. A link between wound healing and the nervous system is clinically apparent as peripheral neuropathy is reported in 30–50% of diabetic patients and is the most common and sensitive predictor of foot ulceration. Indeed, a bidirectional connection between the nervous and the immune systems and its role in wound repair has emerged as one of the focal features of the wound-healing dogma. This review provides a broad overview of the mediators of this connection, which include neuropeptides and cytokines released from nerve fibres, immune cells and cutaneous cells. In-depth understanding of the signalling pathways in the neuroimmune axis in diabetic wound healing is vital to the development of successful wound-healing therapies.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 11 , July 2009 , e2
Copyright
Copyright © Cambridge University Press 2009

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References

References

1[No authors listed] (2008) Economic costs of diabetes in the U.S. in 2007. Diabetes Care 31, 596-615CrossRefGoogle Scholar
2[No authors listed] (1999) Consensus Development Conference on Diabetic Foot Wound Care: 7–8 April 1999, Boston, Massachusetts. American Diabetes Association. Diabetes Care 22, 1354-1360Google Scholar
3Boulton, A.J. et al. (2005) The global burden of diabetic foot disease. Lancet 366, 1719-1724CrossRefGoogle ScholarPubMed
4Edmonds, M.E. et al. (1986) Improved survival of the diabetic foot: the role of a specialized foot clinic. QJM 60, 763-771Google ScholarPubMed
5Thomson, F. et al. (1991) A team approach to diabtic foot care–the Manchester experience. The Foot 1, 75-82CrossRefGoogle Scholar
6Falanga, V. (2005) Wound healing and its impairment in the diabetic foot. Lancet 366, 1736-1743CrossRefGoogle ScholarPubMed
7Bagdade, J.D., Root, R.K. and Bulger, R.J. (1974) Impaired leukocyte function in patients with poorly controlled diabetes. Diabetes 23, 9-15CrossRefGoogle ScholarPubMed
8Nolan, C.M., Beaty, H.N. and Bagdade, J.D. (1978) Further characterization of the impaired bactericidal function of granulocytes in patients with poorly controlled diabetes. Diabetes 27, 889-894CrossRefGoogle ScholarPubMed
9Falanga, V. (1993) Chronic wounds: pathophysiologic and experimental considerations. Journal of Investigative Dermatology 100, 721-725CrossRefGoogle ScholarPubMed
10Claudy, A.L. et al. (1991) Detection of undegraded fibrin and tumor necrosis factor-alpha in venous leg ulcers. Journal of the American Academy of Dermatology 25, 623-627CrossRefGoogle ScholarPubMed
11Loots, M.A. et al. (1998) Differences in cellular infiltrate and extracellular matrix of chronic diabetic and venous ulcers versus acute wounds. Journal of Investigative Dermatology 111, 850-857CrossRefGoogle ScholarPubMed
12Rosner, K. et al. (1995) Immunohistochemical characterization of the cutaneous cellular infiltrate in different areas of chronic leg ulcers. APMIS 103, 293-299CrossRefGoogle ScholarPubMed
13Moore, K., Ruge, F. and Harding, K.G. (1997) T lymphocytes and the lack of activated macrophages in wound margin biopsies from chronic leg ulcers. British Journal of Dermatology 137, 188-194CrossRefGoogle ScholarPubMed
14Herrick, S.E. et al. (1992) Sequential changes in histologic pattern and extracellular matrix deposition during the healing of chronic venous ulcers. American Journal of Pathology 141, 1085-1095Google ScholarPubMed
15Duraisamy, Y. et al. (2001) Effect of glycation on basic fibroblast growth factor induced angiogenesis and activation of associated signal transduction pathways in vascular endothelial cells: possible relevance to wound healing in diabetes. Angiogenesis 4, 277-288CrossRefGoogle ScholarPubMed
16Elenkov, I.J. (2008) Neurohormonal-cytokine interactions: implications for inflammation, common human diseases and well-being. Neurochemistry International 52, 40-51CrossRefGoogle ScholarPubMed
17Engelhardt, E. et al. (1998) Chemokines IL-8, GROalpha, MCP-1, IP-10, and Mig are sequentially and differentially expressed during phase-specific infiltration of leukocyte subsets in human wound healing. American Journal of Pathology 153, 1849-1860CrossRefGoogle ScholarPubMed
18Hebda, P.A., Collins, M.A. and Tharp, M.D. (1993) Mast cell and myofibroblast in wound healing. Dermatologic Clinics 11, 685-696CrossRefGoogle ScholarPubMed
19Trautmann, A. et al. (2000) Mast cell involvement in normal human skin wound healing: expression of monocyte chemoattractant protein-1 is correlated with recruitment of mast cells which synthesize interleukin-4 in vivo. Journal of Pathology 190, 100-1063.0.CO;2-Q>CrossRefGoogle ScholarPubMed
20Riches, D.W.H. (1996) Macrophage involvement in wound repair, remodeling and fibrosis. In The Molecular and Cellular Biology of Wound Repair (Clark, R.A.F., ed.), pp. 95-141, Plenum Press, New York, USAGoogle Scholar
21Sunderkotter, C. et al. (1994) Macrophages and angiogenesis. Journal of Leukocyte Biology 55, 410-422CrossRefGoogle ScholarPubMed
22Guest, C.B. et al. (2008) The implication of proinflammatory cytokines in type 2 diabetes. Frontiers in Bioscience 13, 5187-5194CrossRefGoogle ScholarPubMed
23Hildebrand, F., Pape, H.C. and Krettek, C. (2005) [The importance of cytokines in the posttraumatic inflammatory reaction.] Unfallchirurg 108, 793-794, 796–803 [Article in German]CrossRefGoogle ScholarPubMed
24Belperio, J.A. et al. (2000) CXC chemokines in angiogenesis. Journal of Leukocyte Biology 68, 1-8CrossRefGoogle ScholarPubMed
25Tilg, H. and Moschen, A.R. (2008) Inflammatory mechanisms in the regulation of insulin resistance. Molecular Medicine 14, 222-231CrossRefGoogle ScholarPubMed
26Bogdanski, P. et al. (2007) Influence of insulin therapy on expression of chemokine receptor CCR5 and selected inflammatory markers in patients with type 2 diabetes mellitus. International Journal of Clinical Pharmacology and Therapeutics 45, 563-567CrossRefGoogle Scholar
27Syrenicz, A. et al. (2006) Low-grade systemic inflammation and the risk of type 2 diabetes in obese children and adolescents. Neuroendocrinolology Letters 27, 453-458Google ScholarPubMed
28Rosa, J.S. et al. (2008) Sustained IL-1alpha, IL-4, and IL-6 elevations following correction of hyperglycemia in children with type 1 diabetes mellitus. Pediatric Diabetes 9, 9-16CrossRefGoogle ScholarPubMed
29Devaraj, S. et al. (2006) Increased monocytic activity and biomarkers of inflammation in patients with type 1 diabetes. Diabetes 55, 774-779CrossRefGoogle Scholar
30Dickinson, S. et al. (2008) High-glycemic index carbohydrate increases nuclear factor-kappaB activation in mononuclear cells of young, lean healthy subjects. American Journal of Clinical Nutrition 87, 1188-1193Google ScholarPubMed
31Kempf, K. et al. (2007) The metabolic syndrome sensitizes leukocytes for glucose-induced immune gene expression. Journal of Molecular Medicine 85, 389-396CrossRefGoogle ScholarPubMed
32Fisman, E.Z., Adler, Y. and Tenenbaum, A. (2008) Biomarkers in cardiovascular diabetology: interleukins and matrixins. Advances in Cardiology 45, 44-64CrossRefGoogle ScholarPubMed
33Hatanaka, E. et al. (2006) Neutrophils and monocytes as potentially important sources of proinflammatory cytokines in diabetes. Clinical and Experimental Immunology 146, 443-447CrossRefGoogle ScholarPubMed
34Hand, W.L., Hand, D.L. and Vasquez, Y. (2007) Increased polymorphonuclear leukocyte respiratory burst function in type 2 diabetes. Diabetes Research and Clinical Practice 76, 44-50CrossRefGoogle ScholarPubMed
35Stegenga, M.E. et al. (2008) Effect of acute hyperglycaemia and/or hyperinsulinaemia on proinflammatory gene expression, cytokine production and neutrophil function in humans. Diabetic Medicine 25, 157-164CrossRefGoogle ScholarPubMed
36Alba-Loureiro, T.C. et al. (2006) Diabetes causes marked changes in function and metabolism of rat neutrophils. Journal of Endocrinology 188, 295-303CrossRefGoogle ScholarPubMed
37Mastej, K. and Adamiec, R. (2008) Neutrophil surface expression of CD11b and CD62L in diabetic microangiopathy. Acta Diabetologica 45, 183-190CrossRefGoogle ScholarPubMed
38Marhoffer, W. et al. (1993) Evidence of ex vivo and in vitro impaired neutrophil oxidative burst and phagocytic capacity in type 1 diabetes mellitus. Diabetes Research and Clinical Practice 19, 183-188CrossRefGoogle ScholarPubMed
39Alba-Loureiro, T.C. et al. (2007) Neutrophil function and metabolism in individuals with diabetes mellitus. Brazilian Journal of Medical and Biological Research 40, 1037-1044CrossRefGoogle ScholarPubMed
40Oncul, O. et al. (2007) Effect of the function of polymorphonuclear leukocytes and interleukin-1 beta on wound healing in patients with diabetic foot infections. Journal of Infection 54, 250-256CrossRefGoogle ScholarPubMed
41Ochoa, O., Torres, F.M. and Shireman, P.K. (2007) Chemokines and diabetic wound healing. Vascular 15, 350-355CrossRefGoogle ScholarPubMed
42Shanmugam, N., Ransohoff, R.M. and Natarajan, R. (2006) Interferon-gamma-inducible protein (IP)-10 mRNA stabilized by RNA-binding proteins in monocytes treated with S100b. Journal of Biological Chemistry 281, 31212-31221CrossRefGoogle ScholarPubMed
43Shanmugam, N. et al. (2008) Proinflammatory effects of advanced lipoxidation end products in monocytes. Diabetes 57, 879-888CrossRefGoogle ScholarPubMed
44Galkowska, H., Wojewodzka, U. and Olszewski, W.L. (2006) Chemokines, cytokines, and growth factors in keratinocytes and dermal endothelial cells in the margin of chronic diabetic foot ulcers. Wound Repair and Regeneration 14, 558-565CrossRefGoogle ScholarPubMed
45Laine, P.S. et al. (2007) Palmitic acid induces IP-10 expression in human macrophages via NF-kappaB activation. Biochemical and Biophysical Research Communications 358, 150-155CrossRefGoogle ScholarPubMed
46Maulik, N. and Das, D.K. (2002) Redox signaling in vascular angiogenesis. Free Radical Biology and Medicine 33, 1047-1060CrossRefGoogle ScholarPubMed
47Soneja, A., Drews, M. and Malinski, T. (2005) Role of nitric oxide, nitroxidative and oxidative stress in wound healing. Pharmacological Reports 57 (Suppl), 108-119Google ScholarPubMed
48Lateef, H. et al. (2005) Pretreatment of diabetic rats with lipoic acid improves healing of subsequently-induced abrasion wounds. Archives of Dermatological Research 297, 75-83CrossRefGoogle ScholarPubMed
49Straino, S. et al. (2008) High-mobility group box 1 protein in human and murine skin: involvement in wound healing. Journal of Investigative Dermatology 128, 1545-1553CrossRefGoogle ScholarPubMed
50Corrales, J.J. et al. (2007) Decreased production of inflammatory cytokines by circulating monocytes and dendritic cells in type 2 diabetic men with atherosclerotic complications. Journal of Diabetes and its Complications 21, 41-49CrossRefGoogle ScholarPubMed
51Maruyama, K. et al. (2007) Decreased macrophage number and activation lead to reduced lymphatic vessel formation and contribute to impaired diabetic wound healing. American Journal of Pathology 170, 1178-1191CrossRefGoogle ScholarPubMed
52Urbancic-Rovan, V. (2005) Causes of diabetic foot lesions. Lancet 366, 1675-1676CrossRefGoogle ScholarPubMed
53Sheehan, P. et al. (2003) Percent change in wound area of diabetic foot ulcers over a 4-week period is a robust predictor of complete healing in a 12-week prospective trial. Diabetes Care 26, 1879-1882CrossRefGoogle Scholar
54Young, M.J., Breddy, J.L., Veves, A. and Boulton, A.J. (1994) The prediction of diabetic neuropathic foot ulceration using vibration perception thresholds. A prospective study. Diabetes Care 17, 557-560CrossRefGoogle ScholarPubMed
55Adler, A.I. et al. (1997) Risk factors for diabetic peripheral sensory neuropathy. Results of the Seattle Prospective Diabetic Foot Study. Diabetes Care 20, 1162-1167CrossRefGoogle ScholarPubMed
56Reiber, G.E. et al. (1999) Causal pathways for incident lower-extremity ulcers in patients with diabetes from two settings. Diabetes Care 22, 157-162CrossRefGoogle ScholarPubMed
57Yao, J.S. et al. (2006) Interleukin-6 triggers human cerebral endothelial cells proliferation and migration: the role for KDR and MMP-9. Biochemical and Biophysical Research Communications 342, 1396-1404CrossRefGoogle ScholarPubMed
58Vinik, A.I. et al. (2000) Diabetic neuropathies. Diabetologia 43, 957-973CrossRefGoogle ScholarPubMed
59Lindberger, M. et al. (1989) Nerve fibre studies in skin biopsies in peripheral neuropathies. I. Immunohistochemical analysis of neuropeptides in diabetes mellitus. Journal of the Neurological Sciences 93, 289-296CrossRefGoogle ScholarPubMed
60Galkowska, H. et al. (2006) Neurogenic factors in the impaired healing of diabetic foot ulcers. Journal of Surgical Research 134, 252-258CrossRefGoogle ScholarPubMed
61Quattrini, C., Jeziorska, M. and Malik, R.A. (2004) Small fiber neuropathy in diabetes: clinical consequence and assessment. The International Journal of Lower Extremity Wounds 3, 16-21CrossRefGoogle ScholarPubMed
62Luger, T.A. (2002) Neuromediators–a crucial component of the skin immune system. Journal of Dermatological Science 30, 87-93CrossRefGoogle ScholarPubMed
63Berczi, I. et al. (1996) The immune effects of neuropeptides. Baillieres Clinical Rheumatology 10, 227-257CrossRefGoogle ScholarPubMed
64Krishnan, S.T. et al. (2007) Neurovascular factors in wound healing in the foot skin of type 2 diabetic subjects. Diabetes Care 30, 3058-3062CrossRefGoogle ScholarPubMed
65Pomposelli, F.B. et al. (2003) A decade of experience with dorsalis pedis artery bypass: analysis of outcome in more than 1000 cases. Journal of Vascular Surgery 37, 307-315CrossRefGoogle ScholarPubMed
66Vareniuk, I., Pavlov, I.A. and Obrosova, I.G. (2008) Inducible nitric oxide synthase gene deficiency counteracts multiple manifestations of peripheral neuropathy in a streptozotocin-induced mouse model of diabetes. Diabetologia 51, 2126-2133CrossRefGoogle Scholar
67Obrosova, I.G. et al. (2005) Oxidative-nitrosative stress and poly(ADP-ribose) polymerase (PARP) activation in experimental diabetic neuropathy: the relation is revisited. Diabetes 54, 3435-3441CrossRefGoogle ScholarPubMed
68Kellogg, A.P. et al. (2007) Protective effects of cyclooxygenase-2 gene inactivation against peripheral nerve dysfunction and intraepidermal nerve fiber loss in experimental diabetes. Diabetes 56, 2997-3005CrossRefGoogle ScholarPubMed
69Obrosova, I.G. et al. (2007) High-fat diet induced neuropathy of pre-diabetes and obesity: effects of “healthy” diet and aldose reductase inhibition. Diabetes 56, 2598-2608CrossRefGoogle ScholarPubMed
70Roosterman, D. et al. (2006) Neuronal control of skin function: the skin as a neuroimmunoendocrine organ. Physiological Reviews 86, 1309-1379CrossRefGoogle ScholarPubMed
71Nakamura, M. et al. (2003) Promotion of corneal epithelial wound healing in diabetic rats by the combination of a substance P-derived peptide (FGLM-NH2) and insulin-like growth factor-1. Diabetologia 46, 839-842CrossRefGoogle ScholarPubMed
72Movafagh, S. et al. (2006) Neuropeptide Y induces migration, proliferation, and tube formation of endothelial cells bimodally via Y1, Y2, and Y5 receptors. The FASEB Journal 20, 1924-1926CrossRefGoogle ScholarPubMed
73Ekstrand, A.J. et al. (2003) Deletion of neuropeptide Y (NPY) 2 receptor in mice results in blockage of NPY-induced angiogenesis and delayed wound healing. Proceedings of the National Academy of Sciences of the United States of America 100, 6033-6038CrossRefGoogle ScholarPubMed
74Kuo, L.E., Abe, K. and Zukowska, Z. (2007) Stress, NPY and vascular remodeling: Implications for stress-related diseases. Peptides 28, 435-440CrossRefGoogle ScholarPubMed
75Delgado, A.V., McManus, A.T. and Chambers, J.P. (2005) Exogenous administration of Substance P enhances wound healing in a novel skin-injury model. Experimental Biology and Medicine 230, 271-280CrossRefGoogle Scholar
76Zukowska, Z., Grant, D.S. and Lee, E.W. (2003) Neuropeptide Y: a novel mechanism for ischemic angiogenesis. Trends in Cardiovascular Medicine 13, 86-92CrossRefGoogle ScholarPubMed
77Hokfelt, T. et al. (1975) Experimental immunohistochemical studies on the localization and distribution of substance P in cat primary sensory neurons. Brain Research 100, 235-252CrossRefGoogle ScholarPubMed
78Hokfelt, T. et al. (1975) Substance p: localization in the central nervous system and in some primary sensory neurons. Science 190, 889-890CrossRefGoogle ScholarPubMed
79Maggi, C.A. (2000) The troubled story of tachykinins and neurokinins. Trends in Pharmacological Sciences 21, 173-175CrossRefGoogle ScholarPubMed
80Maggi, C.A. (1995) The mammalian tachykinin receptors. General Pharmacology 26, 911-944CrossRefGoogle ScholarPubMed
81Khawaja, A.M. and Rogers, D.F. (1996) Tachykinins: receptor to effector. International Journal of Biochemistry and Cell Biology 28, 721-738CrossRefGoogle ScholarPubMed
82Harrison, S. and Geppetti, P. (2001) Substance P. International Journal of Biochemistry and Cell Biology 33, 555-576CrossRefGoogle ScholarPubMed
83Kunt, T. et al. (2000) Serum levels of substance P are decreased in patients with type 1 diabetes. Experimental and Clinical Endocrinology and Diabetes 108, 164-167CrossRefGoogle ScholarPubMed
84Olerud, J.E. et al. (1999) Neutral endopeptidase expression and distribution in human skin and wounds. Journal of Investigative Dermatology 112, 873-881CrossRefGoogle ScholarPubMed
85Bou-Gharios, G. et al. (1995) Expression of ectopeptidases in scleroderma. Annals of the Rheumatic Diseases 54, 111-116CrossRefGoogle ScholarPubMed
86Antezana, M. et al. (2002) Neutral endopeptidase activity is increased in the skin of subjects with diabetic ulcers. Journal of Investigative Dermatology 119, 1400-1404CrossRefGoogle ScholarPubMed
87Spenny, M.L. et al. (2002) Neutral endopeptidase inhibition in diabetic wound repair. Wound Repair and Regeneration 10, 295-301CrossRefGoogle ScholarPubMed
88Pernow, B. (1983) Substance P. Pharmacological Reviews 35, 85-141Google ScholarPubMed
89Ho, W.Z. et al. (1997) Human monocytes and macrophages express substance P and neurokinin-1 receptor. Journal of Immunology 159, 5654-5660CrossRefGoogle ScholarPubMed
90Lai, J.P., Douglas, S.D. and Ho, W.Z. (1998) Human lymphocytes express substance P and its receptor. Journal of Neuroimmunology 86, 80-86CrossRefGoogle ScholarPubMed
91Lai, J.P. et al. (2002) Quantification of substance p mRNA in human immune cells by real-time reverse transcriptase PCR assay. Clinical and Diagnostic Laboratory Immunology 9, 138-143Google ScholarPubMed
92Lambrecht, B.N. (2001) Immunologists getting nervous: neuropeptides, dendritic cells and T cell activation. Respiratory Research 2, 133-138CrossRefGoogle ScholarPubMed
93Lambrecht, B.N. et al. (1999) Endogenously produced substance P contributes to lymphocyte proliferation induced by dendritic cells and direct TCR ligation. European Journal of Immunology 29, 3815-38253.0.CO;2-#>CrossRefGoogle ScholarPubMed
94Weinstock, J.V. et al. (1988) Eosinophils from granulomas in murine schistosomiasis mansoni produce substance P. Journal of Immunology 141, 961-966CrossRefGoogle ScholarPubMed
95O'Connor, T.M. et al. (2004) The role of substance P in inflammatory disease. Journal of Cellular Physiology 201, 167-180CrossRefGoogle ScholarPubMed
96Schratzberger, P. et al. (1997) Differential chemotactic activities of sensory neuropeptides for human peripheral blood mononuclear cells. Journal of Immunology 158, 3895-3901CrossRefGoogle ScholarPubMed
97Delgado, A.V., McManus, A.T. and Chambers, J.P. (2003) Production of tumor necrosis factor-alpha, interleukin 1-beta, interleukin 2, and interleukin 6 by rat leukocyte subpopulations after exposure to substance P. Neuropeptides 37, 355-361CrossRefGoogle ScholarPubMed
98Matis, W.L., Lavker, R.M. and Murphy, G.F. (1990) Substance P induces the expression of an endothelial-leukocyte adhesion molecule by microvascular endothelium. Journal of Investigative Dermatology 94, 492-495CrossRefGoogle ScholarPubMed
99Vishwanath, R. and Mukherjee, R. (1996) Substance P promotes lymphocyte-endothelial cell adhesion preferentially via LFA-1/ICAM-1 interactions. Journal of Neuroimmunology 71, 163-171CrossRefGoogle ScholarPubMed
100Quinlan, K.L. et al. (1999) Substance P activates coincident NF-AT- and NF-kappa B-dependent adhesion molecule gene expression in microvascular endothelial cells through intracellular calcium mobilization. Journal of Immunology 163, 5656-5665CrossRefGoogle ScholarPubMed
101Bulut, K. et al. (2008) Sensory neuropeptides and epithelial cell restitution: the relevance of SP- and CGRP-stimulated mast cells. International Journal of Colorectal Disease 23, 535-541CrossRefGoogle ScholarPubMed
102Felderbauer, P. et al. (2007) Substance P induces intestinal wound healing via fibroblasts–evidence for a TGF-beta-dependent effect. International Journal of Colorectal Disease 22, 1475-1480CrossRefGoogle ScholarPubMed
103Seegers, H.C. et al. (2003) Enhancement of angiogenesis by endogenous substance P release and neurokinin-1 receptors during neurogenic inflammation. Journal of Pharmacology and Experimental Therapeutics 306, 8-12CrossRefGoogle ScholarPubMed
104Burssens, P. et al. (2005) Exogenously administered substance P and neutral endopeptidase inhibitors stimulate fibroblast proliferation, angiogenesis and collagen organization during Achilles tendon healing. Foot and Ankle International 26, 832-839CrossRefGoogle ScholarPubMed
105Gibran, N.S. et al. (2002) Diminished neuropeptide levels contribute to the impaired cutaneous healing response associated with diabetes mellitus. Journal of Surgical Research 108, 122-128CrossRefGoogle Scholar
106Blomqvist, A.G. and Herzog, H. (1997) Y-receptor subtypes–how many more? Trends in Neurosciences 20, 294-298CrossRefGoogle ScholarPubMed
107Ericsson, A. et al. (1987) Detection of neuropeptide Y and its mRNA in megakaryocytes: enhanced levels in certain autoimmune mice. Proceedings of the National Academy of Sciences of the United States of America 84, 5585-5589CrossRefGoogle ScholarPubMed
108Strand, F.L. (1999) Neuropeptides: Regulators of Physiological Processes, MIT Press, Cambridge, MA, USAGoogle Scholar
109Larhammar, D. (1996) Structural diversity of receptors for neuropeptide Y, peptide YY and pancreatic polypeptide. Regulatory Peptides 65, 165-174CrossRefGoogle ScholarPubMed
110Franco-Cereceda, A., Lundberg, J.M. and Dahlof, C. (1985) Neuropeptide Y and sympathetic control of heart contractility and coronary vascular tone. Acta Physiologica Scandinavica 124, 361-369CrossRefGoogle ScholarPubMed
111Erlinge, D., Brunkwall, J. and Edvinsson, L. (1994) Neuropeptide Y stimulates proliferation of human vascular smooth muscle cells: cooperation with noradrenaline and ATP. Regulatory Peptides 50, 259-265CrossRefGoogle ScholarPubMed
112Zukowska-Grojec, Z. et al. (1993) Mitogenic effect of neuropeptide Y in rat vascular smooth muscle cells. Peptides 14, 263-268CrossRefGoogle ScholarPubMed
113Frankish, H.M. et al. (1995) Neuropeptide Y, the hypothalamus, and diabetes: insights into the central control of metabolism. Peptides 16, 757-771CrossRefGoogle ScholarPubMed
114Ahlborg, G. and Lundberg, J.M. (1996) Exercise-induced changes in neuropeptide Y, noradrenaline and endothelin-1 levels in young people with type I diabetes. Clinical Physiology 16, 645-655CrossRefGoogle ScholarPubMed
115Wallengren, J. et al. (1995) Innervation of the skin of the forearm in diabetic patients: relation to nerve function. Acta Dermato-Venereologica 75, 37-42CrossRefGoogle ScholarPubMed
116Levy, D.M. et al. (1989) Depletion of cutaneous nerves and neuropeptides in diabetes mellitus: an immunocytochemical study. Diabetologia 32, 427-433CrossRefGoogle ScholarPubMed
117Kuncova, J. et al. (2005) Heterogenous changes in neuropeptide Y, norepinephrine and epinephrine concentrations in the hearts of diabetic rats. Autonomic Neuroscience 121, 7-15CrossRefGoogle ScholarPubMed
118Andersson, D. et al. (1992) Diminished contractile responses to neuropeptide Y of arteries from diabetic rabbits. Journal of the Autonomic Nervous System 37, 215-222CrossRefGoogle ScholarPubMed
119Wheway, J., Herzog, H. and Mackay, F. (2007) NPY and receptors in immune and inflammatory diseases. Current Topics in Medicinal Chemistry 7, 1743-1752CrossRefGoogle ScholarPubMed
120Groneberg, D.A. et al. (2004) Neuropeptide Y (NPY). Pulmonary Pharmacology and Therapeutics 17, 173-180CrossRefGoogle ScholarPubMed
121Bedoui, S. et al. (2003) Relevance of neuropeptide Y for the neuroimmune crosstalk. Journal of Neuroimmunology 134, 1-11CrossRefGoogle ScholarPubMed
122Salo, P. et al. (2007) Neuropeptides regulate expression of matrix molecule, growth factor and inflammatory mediator mRNA in explants of normal and healing medial collateral ligament. Regulatory Peptides 142, 1-6CrossRefGoogle ScholarPubMed
123Ghersi, G. et al. (2001) Critical role of dipeptidyl peptidase IV in neuropeptide Y-mediated endothelial cell migration in response to wounding. Peptides 22, 453-458CrossRefGoogle ScholarPubMed
124Marion-Audibert, A.M. et al. (2000) [Effects of endocrine peptides on proliferation, migration and differentiation of human endothelial cells.] Gastroenterologie Clinique et Biologique 24, 644-648 [Article in French]Google ScholarPubMed
125Zukowska-Grojec, Z. et al. (1998) Neuropeptide Y: a novel angiogenic factor from the sympathetic nerves and endothelium. Circulation Research 83, 187-195CrossRefGoogle ScholarPubMed
126Kitlinska, J. et al. (2005) Differential effects of neuropeptide Y on the growth and vascularization of neural crest-derived tumors. Cancer Research 65, 1719-1728CrossRefGoogle ScholarPubMed
127Zukowska, Z. et al. (2003) Neuropeptide Y: a new mediator linking sympathetic nerves, blood vessels and immune system? Canadian Journal of Physiology and Pharmacology 81, 89-94CrossRefGoogle ScholarPubMed
128Kitlinska, J. et al. (2002) Neuropeptide Y-induced angiogenesis in aging. Peptides 23, 71-77CrossRefGoogle ScholarPubMed
129van Rossum, D., Hanisch, U.K. and Quirion, R. (1997) Neuroanatomical localization, pharmacological characterization and functions of CGRP, related peptides and their receptors. Neuroscience and Biobehavioral Reviews 21, 649-678CrossRefGoogle ScholarPubMed
130Holzer, P. (1988) Local effector functions of capsaicin-sensitive sensory nerve endings: involvement of tachykinins, calcitonin gene-related peptide and other neuropeptides. Neuroscience 24, 739-768CrossRefGoogle ScholarPubMed
131Maggi, C.A. (1995) Tachykinins and calcitonin gene-related peptide (CGRP) as co-transmitters released from peripheral endings of sensory nerves. Progress in Neurobiology 45, 1-98CrossRefGoogle ScholarPubMed
132Russwurm, S. et al. (2001) Procalcitonin and CGRP-1 mrna expression in various human tissues. Shock 16, 109-112CrossRefGoogle ScholarPubMed
133Hay, D.L., Poyner, D.R. and Quirion, R. (2008) International Union of Pharmacology. LXIX. Status of the calcitonin gene-related peptide subtype 2 receptor. Pharmacological Reviews 60, 143-145CrossRefGoogle ScholarPubMed
134Song, J.X. et al. (2008) Impaired transient receptor potential vanilloid 1 in streptozotocin-induced diabetic hearts. International Journal of Cardiology Mar 29; [Epub ahead of print]Google ScholarPubMed
135Dux, M. et al. (2007) Loss of capsaicin-induced meningeal neurogenic sensory vasodilatation in diabetic rats. Neuroscience 150, 194-201CrossRefGoogle ScholarPubMed
136Adeghate, E. et al. (2006) Pattern of distribution of calcitonin gene-related Peptide in the dorsal root ganglion of animal models of diabetes mellitus. Annals of the New York Academy of Sciences 1084, 296-303CrossRefGoogle ScholarPubMed
137Oltman, C.L. et al. (2008) Vascular and neural dysfunction in Zucker diabetic fatty rats: a difficult condition to reverse. Diabetes, Obesity and Metabolism 10, 64-74CrossRefGoogle ScholarPubMed
138Oltman, C.L. et al. (2008) Treatment of Zucker diabetic fatty rats with AVE7688 improves vascular and neural dysfunction. Diabetes, Obesity and Metabolism Jun 16; [Epub ahead of print]CrossRefGoogle Scholar
139Sheykhzade, M. et al. (2000) The effect of long-term streptozotocin-induced diabetes on contractile and relaxation responses of coronary arteries: selective attenuation of CGRP-induced relaxations. British Journal of Pharmacology 129, 1212-1218CrossRefGoogle ScholarPubMed
140Chottova Dvorakova, M. et al. (2005) Cardiomyopathy in streptozotocin-induced diabetes involves intra-axonal accumulation of calcitonin gene-related peptide and altered expression of its receptor in rats. Neuroscience 134, 51-58CrossRefGoogle ScholarPubMed
141Yorek, M.A. et al. (2004) Sensory nerve innervation of epineurial arterioles of the sciatic nerve containing calcitonin gene-related peptide: effect of streptozotocin-induced diabetes. Experimental Diabesity Research 5, 187-193CrossRefGoogle ScholarPubMed
142Ambalavanar, R. et al. (2006) Muscle inflammation induces a rapid increase in calcitonin gene-related peptide (CGRP) mRNA that temporally relates to CGRP immunoreactivity and nociceptive behavior. Neuroscience 143, 875-884CrossRefGoogle ScholarPubMed
143Ambalavanar, R. et al. (2006) Deep tissue inflammation upregulates neuropeptides and evokes nociceptive behaviors which are modulated by a neuropeptide antagonist. Pain 120, 53-68CrossRefGoogle ScholarPubMed
144Hu, C.L., Xiang, J.Z. and Hu, F.F. (2008) Vanilloid receptor TRPV1, sensory C-fibers, and activation of adventitial mast cells A novel mechanism involved in adventitial inflammation. Medical Hypotheses 71, 102-103CrossRefGoogle ScholarPubMed
145Linscheid, P. et al. (2004) Expression and secretion of procalcitonin and calcitonin gene-related peptide by adherent monocytes and by macrophage-activated adipocytes. Critical Care Medicine 32, 1715-1721CrossRefGoogle ScholarPubMed
146Linscheid, P. et al. (2005) Autocrine/paracrine role of inflammation-mediated calcitonin gene-related peptide and adrenomedullin expression in human adipose tissue. Endocrinology 146, 2699-2708CrossRefGoogle ScholarPubMed
147Dallos, A. et al. (2006) Effects of the neuropeptides substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide and galanin on the production of nerve growth factor and inflammatory cytokines in cultured human keratinocytes. Neuropeptides 40, 251-263CrossRefGoogle ScholarPubMed
148Wang, F. et al. (1992) Calcitonin gene-related peptide inhibits interleukin 2 production by murine T lymphocytes. Journal of Biological Chemistry 267, 21052-21057CrossRefGoogle ScholarPubMed
149Foster, C.A. et al. (1992) Calcitonin gene-related peptide is chemotactic for human T lymphocytes. Annals of the New York Academy of Sciences 657, 397-404CrossRefGoogle ScholarPubMed
150Zhang, J.S. et al. (2006) Regulatory peptides modulate adhesion of polymorphonuclear leukocytes to bronchial epithelial cells through regulation of interleukins, ICAM-1 and NF-kappaB/IkappaB. Acta Biochimica et Biophysica Sinica 38, 119-128CrossRefGoogle ScholarPubMed
151Tran, M.T. et al. (2000) Calcitonin gene-related peptide induces IL-8 synthesis in human corneal epithelial cells. Journal of Immunology 164, 4307-4312CrossRefGoogle ScholarPubMed
152Yamaguchi, M. et al. (2004) Neuropeptides stimulate production of interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha in human dental pulp cells. Inflammation Research 53, 199-204CrossRefGoogle ScholarPubMed
153Yaraee, R. et al. (2003) Neuropeptides (SP and CGRP) augment pro-inflammatory cytokine production in HSV-infected macrophages. International Immunopharmacology 3, 1883-1887CrossRefGoogle ScholarPubMed
154Toda, M. et al. (2008) Roles of calcitonin gene-related peptide in facilitation of wound healing and angiogenesis. Biomedicine and Pharmacotherapy 62, 352-359CrossRefGoogle ScholarPubMed
155Haegerstrand, A. et al. (1990) Calcitonin gene-related peptide stimulates proliferation of human endothelial cells. Proceedings of the National Academy of Sciences of the United States of America 87, 3299-3303CrossRefGoogle ScholarPubMed
156Richard, D., Huang, Q. and Timofeeva, E. (2000) The corticotropin-releasing hormone system in the regulation of energy balance in obesity. International Journal of Obesity and Related Metabolic Disorders 24 Suppl 2, S36-39CrossRefGoogle ScholarPubMed
157Baigent, S.M. (2001) Peripheral corticotropin-releasing hormone and urocortin in the control of the immune response. Peptides 22, 809-820CrossRefGoogle ScholarPubMed
158Carlin, K.M., Vale, W.W. and Bale, T.L. (2006) Vital functions of corticotropin-releasing factor (CRF) pathways in maintenance and regulation of energy homeostasis. Proceedings of the National Academy of Sciences of the United States of America 103, 3462-3467CrossRefGoogle ScholarPubMed
159Perrin, M.H. and Vale, W.W. (1999) Corticotropin releasing factor receptors and their ligand family. Annals of the New York Academy of Sciences 885, 312-328CrossRefGoogle ScholarPubMed
160Chiodini, I. et al. (2005) Association of subclinical hypercortisolism with type 2 diabetes mellitus: a case-control study in hospitalized patients. European Journal of Endocrinology 153, 837-844CrossRefGoogle ScholarPubMed
161Ghizzoni, L. et al. (1993) Adrenal steroid and adrenocorticotropin responses to human corticotropin-releasing hormone stimulation test in adolescents with type I diabetes mellitus. Metabolism 42, 1141-1145CrossRefGoogle ScholarPubMed
162Roy, M.S. et al. (1993) The ovine corticotropin-releasing hormone-stimulation test in type I diabetic patients and controls: suggestion of mild chronic hypercortisolism. Metabolism 42, 696-700CrossRefGoogle ScholarPubMed
163Chan, O. et al. (2002) Hyperactivation of the hypothalamo-pituitary-adrenocortical axis in streptozotocin-diabetes is associated with reduced stress responsiveness and decreased pituitary and adrenal sensitivity. Endocrinology 143, 1761-1768CrossRefGoogle ScholarPubMed
164Chan, O. et al. (2005) Hyperglycemia does not increase basal hypothalamo-pituitary-adrenal activity in diabetes but it does impair the HPA response to insulin-induced hypoglycemia. American Journal of Physiology – Regulatory, Integrative and Comparative Physiology 289, R235-246CrossRefGoogle Scholar
165Chan, O. et al. (2002) Diabetes impairs hypothalamo-pituitary-adrenal (HPA) responses to hypoglycemia, and insulin treatment normalizes HPA but not epinephrine responses. Diabetes 51, 1681-1689CrossRefGoogle Scholar
166Turnbull, A.V. and Rivier, C.L. (1999) Sprague-Dawley rats obtained from different vendors exhibit distinct adrenocorticotropin responses to inflammatory stimuli. Neuroendocrinology 70, 186-195CrossRefGoogle ScholarPubMed
167Lozovaya, N. and Miller, A.D. (2003) Chemical neuroimmunology: health in a nutshell bidirectional communication between immune and stress (limbic-hypothalamic-pituitary-adrenal) systems. Chembiochem 4, 466-484CrossRefGoogle Scholar
168Chrousos, G.P. (1995) The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. New England Journal of Medicine 332, 1351-1362CrossRefGoogle ScholarPubMed
169Elenkov, I.J. et al. (1999) Stress, corticotropin-releasing hormone, glucocorticoids, and the immune/inflammatory response: acute and chronic effects. Annals of the New York Academy of Sciences 876, 1-11; discussion 11–13CrossRefGoogle ScholarPubMed
170Elenkov, I.J. and Chrousos, G.P. (1999) Stress Hormones, Th1/Th2 patterns, Pro/Anti-inflammatory Cytokines and Susceptibility to Disease. Trends in Endocrinology and Metabolism 10, 359-368CrossRefGoogle ScholarPubMed
171Webster, E.L., Elenkov, I.J. and Chrousos, G.P. (1997) Corticotropin-releasing hormone acts on immune cells to elicit pro-inflammatory responses. Molecular Psychiatry 2, 345-346CrossRefGoogle ScholarPubMed
172Monney, L. et al. (2002) Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. Nature 415, 536-541CrossRefGoogle ScholarPubMed
173Brown, D.H. and Zwilling, B.S. (1994) Activation of the hypothalamic-pituitary-adrenal axis differentially affects the anti-mycobacterial activity of macrophages from BCG-resistant and susceptible mice. Journal of Neuroimmunology 53, 181-187CrossRefGoogle ScholarPubMed
174Sheridan, J.F. et al. (1998) Stress-induced neuroendocrine modulation of viral pathogenesis and immunity. Annals of the New York Academy of Sciences 840, 803-808CrossRefGoogle ScholarPubMed
175Webster, E.L. et al. (1998) Corticotropin-releasing hormone and inflammation. Annals of the New York Academy of Sciences 840, 21-32CrossRefGoogle ScholarPubMed
176Karalis, K. et al. (1997) CRH and the immune system. Journal of Neuroimmunology 72, 131-136CrossRefGoogle ScholarPubMed
177Theoharides, T.C. et al. (1998) Corticotropin-releasing hormone induces skin mast cell degranulation and increased vascular permeability, a possible explanation for its proinflammatory effects. Endocrinology 139, 403-413CrossRefGoogle ScholarPubMed
178Karalis, K. et al. (1991) Autocrine or paracrine inflammatory actions of corticotropin-releasing hormone in vivo. Science 254, 421-423CrossRefGoogle ScholarPubMed
179Crofford, L.J. et al. (1993) Corticotropin-releasing hormone in synovial fluids and tissues of patients with rheumatoid arthritis and osteoarthritis. Journal of Immunology 151, 1587-1596CrossRefGoogle ScholarPubMed
180Glasper, E.R. and Devries, A.C. (2005) Social structure influences effects of pair-housing on wound healing. Brain, Behavior, and Immunity 19, 61-68CrossRefGoogle ScholarPubMed
181Detillion, C.E. et al. (2004) Social facilitation of wound healing. Psychoneuroendocrinology 29, 1004-1011CrossRefGoogle ScholarPubMed
182Kalin, N.H. et al. (2006) Stress decreases, while central nucleus amygdala lesions increase, IL-8 and MIP-1alpha gene expression during tissue healing in non-human primates. Brain, Behavior, and Immunity 20, 564-568CrossRefGoogle ScholarPubMed
183Head, C.C. et al. (2006) Androstenediol reduces the anti-inflammatory effects of restraint stress during wound healing. Brain, Behavior, and Immunity 20, 590-596CrossRefGoogle ScholarPubMed
184Mercado, A.M. et al. (2002) Altered kinetics of IL-1 alpha, IL-1 beta, and KGF-1 gene expression in early wounds of restrained mice. Brain, Behavior, and Immunity 16, 150-162CrossRefGoogle ScholarPubMed
185Rojas, I.G. et al. (2002) Stress-induced susceptibility to bacterial infection during cutaneous wound healing. Brain, Behavior, and Immunity 16, 74-84CrossRefGoogle ScholarPubMed
186Gantz, I. and Fong, T.M. (2003) The melanocortin system. American Journal of Physiology – Endocrinology and Metabolism 284, E468-474CrossRefGoogle ScholarPubMed
187Seidah, N.G. et al. (1999) The subtilisin/kexin family of precursor convertases. Emphasis on PC1, PC2/7B2, POMC and the novel enzyme SKI-1. Annals of the New York Academy of Sciences 885, 57-74CrossRefGoogle ScholarPubMed
188Thody, A.J. et al. (1983) MSH peptides are present in mammalian skin. Peptides 4, 813-816CrossRefGoogle ScholarPubMed
189Slominski, A. et al. (1993) Detection of proopiomelanocortin-derived antigens in normal and pathologic human skin. Journal of Laboratory and Clinical Medicine 122, 658-666Google ScholarPubMed
190Mazurkiewicz, J.E., Corliss, D. and Slominski, A. (2000) Spatiotemporal expression, distribution, and processing of POMC and POMC-derived peptides in murine skin. Journal of Histochemistry and Cytochemistry 48, 905-914CrossRefGoogle ScholarPubMed
191Bohm, M. et al. (2006) Melanocortin receptor ligands: new horizons for skin biology and clinical dermatology. Journal of Investigative Dermatology 126, 1966-1975CrossRefGoogle ScholarPubMed
192Bhardwaj, R. et al. (1997) Evidence for the differential expression of the functional alpha-melanocyte-stimulating hormone receptor MC-1 on human monocytes. Journal of Immunology 158, 3378-3384CrossRefGoogle ScholarPubMed
193Hochgeschwender, U. et al. (2003) Altered glucose homeostasis in proopiomelanocortin-null mouse mutants lacking central and peripheral melanocortin. Endocrinology 144, 5194-5202CrossRefGoogle ScholarPubMed
194Fan, W. et al. (2000) The central melanocortin system can directly regulate serum insulin levels. Endocrinology 141, 3072-3079CrossRefGoogle ScholarPubMed
195Lee, M. et al. (2007) Transgenic MSH overexpression attenuates the metabolic effects of a high-fat diet. American Journal of Physiology – Endocrinology and Metabolism 293, E121-131CrossRefGoogle ScholarPubMed
196Kim, E.M. et al. (1999) STZ-induced diabetes decreases and insulin normalizes POMC mRNA in arcuate nucleus and pituitary in rats. American Journal of Physiology 276, R1320-1326Google ScholarPubMed
197Havel, P.J. et al. (2000) Effects of streptozotocin-induced diabetes and insulin treatment on the hypothalamic melanocortin system and muscle uncoupling protein 3 expression in rats. Diabetes 49, 244-252CrossRefGoogle ScholarPubMed
198Abou-Mohamed, G. et al. (1995) HP-228, a novel synthetic peptide, inhibits the induction of nitric oxide synthase in vivo but not in vitro. Journal of Pharmacology and Experimental Therapeutics 275, 584-591Google Scholar
199Rajora, N. et al. (1997) alpha-MSH modulates local and circulating tumor necrosis factor-alpha in experimental brain inflammation. Journal of Neuroscience 17, 2181-2186CrossRefGoogle ScholarPubMed
200Rajora, N. et al. (1997) alpha-MSH modulates experimental inflammatory bowel disease. Peptides 18, 381-385CrossRefGoogle ScholarPubMed
201Catania, A. et al. (1999) alpha-MSH in systemic inflammation. Central and peripheral actions. Annals of the New York Academy of Sciences 885, 183-187CrossRefGoogle ScholarPubMed
202Gatti, S. et al. (2002) alpha-Melanocyte-stimulating hormone protects the allograft in experimental heart transplantation. Transplantation 74, 1678-1684CrossRefGoogle ScholarPubMed
203Catania, A. et al. (2004) Targeting melanocortin receptors as a novel strategy to control inflammation. Pharmacological Reviews 56, 1-29CrossRefGoogle ScholarPubMed
204Bohm, M. et al. (1999) Alpha-melanocyte-stimulating hormone modulates activation of NF-kappa B and AP-1 and secretion of interleukin-8 in human dermal fibroblasts. Annals of the New York Academy of Sciences 885, 277-286CrossRefGoogle ScholarPubMed
205Bhardwaj, R.S. et al. (1996) Pro-opiomelanocortin-derived peptides induce IL-10 production in human monocytes. Journal of Immunology 156, 2517-2521CrossRefGoogle ScholarPubMed
206Taherzadeh, S. et al. (1999) alpha-MSH and its receptors in regulation of tumor necrosis factor-alpha production by human monocyte/macrophages. American Journal of Physiology 276, R1289-1294Google ScholarPubMed
207Catania, A. et al. (2000) Plasma concentrations and anti-L-cytokine effects of alpha-melanocyte stimulating hormone in septic patients. Critical Care Medicine 28, 1403-1407CrossRefGoogle ScholarPubMed
208Star, R.A. et al. (1995) Evidence of autocrine modulation of macrophage nitric oxide synthase by alpha-melanocyte-stimulating hormone. Proceedings of the National Academy of Sciences of the United States of America 92, 8016-8020CrossRefGoogle ScholarPubMed
209Mandrika, I., Muceniece, R. and Wikberg, J.E. (2001) Effects of melanocortin peptides on lipopolysaccharide/interferon-gamma-induced NF-kappaB DNA binding and nitric oxide production in macrophage-like RAW 264.7 cells: evidence for dual mechanisms of action. Biochemical Pharmacology 61, 613-621CrossRefGoogle ScholarPubMed
210Kalden, D.H. et al. (1999) Mechanisms of the antiinflammatory effects of alpha-MSH. Role of transcription factor NF-kappa B and adhesion molecule expression. Annals of the New York Academy of Sciences 885, 254-261CrossRefGoogle ScholarPubMed
211Hartmeyer, M. et al. (1997) Human dermal microvascular endothelial cells express the melanocortin receptor type 1 and produce increased levels of IL-8 upon stimulation with alpha-melanocyte-stimulating hormone. Journal of Immunology 159, 1930-1937CrossRefGoogle ScholarPubMed
212Redondo, P. et al. (1998) Alpha-MSH regulates interleukin-10 expression by human keratinocytes. Archives of Dermatological Research 290, 425-428CrossRefGoogle ScholarPubMed
213Bonfiglio, V. et al. (2006) Effects of the COOH-terminal tripeptide alpha-MSH(11–13) on corneal epithelial wound healing: role of nitric oxide. Experimental Eye Research 83, 1366-1372CrossRefGoogle ScholarPubMed
214Evers, B.M. (2006) Neurotensin and growth of normal and neoplastic tissues. Peptides 27, 2424-2433CrossRefGoogle ScholarPubMed
215Gross, K.J. and Pothoulakis, C. (2007) Role of neuropeptides in inflammatory bowel disease. Inflammatory Bowel Diseases 13, 918-932CrossRefGoogle ScholarPubMed
216St-Gelais, F., Jomphe, C. and Trudeau, L.E. (2006) The role of neurotensin in central nervous system pathophysiology: what is the evidence? Journal of Psychiatry and Neuroscience 31, 229-245Google ScholarPubMed
217Sheppard, M.C. et al. (1985) Immunoreactive neurotensin in spontaneous syndromes of obesity and diabetes in mice. Acta Endocrinologica 108, 532-536Google ScholarPubMed
218Berelowitz, M. and Frohman, L.A. (1982) The role of neurotensin in the regulation of carbohydrate metabolism and in diabetes. Annals of the New York Academy of Sciences 400, 150-159CrossRefGoogle ScholarPubMed
219Fernstrom, M.H. et al. (1981) Immunoreactive neurotensin levels in pancreas: elevation in diabetic rats and mice. Metabolism 30, 853-855CrossRefGoogle ScholarPubMed
220El-Salhy, M. (1998) Neuroendocrine peptides of the gastrointestinal tract of an animal model of human type 2 diabetes mellitus. Acta Diabetologica 35, 194-198CrossRefGoogle ScholarPubMed
221Service, F.J. et al. (1986) Neurotensin in diabetes and obesity. Regulatory Peptides 14, 85-92CrossRefGoogle ScholarPubMed
222Goldman, R. et al. (1982) Enhancement of phagocytosis by neurotensin, a newly found biological activity of the neuropeptide. Advances in Experimental Medicine and Biology 155, 133-141CrossRefGoogle ScholarPubMed
223Koff, W.C. and Dunegan, M.A. (1985) Modulation of macrophage-mediated tumoricidal activity by neuropeptides and neurohormones. Journal of Immunology 135, 350-354CrossRefGoogle ScholarPubMed
224Lemaire, I. (1988) Neurotensin enhances IL-1 production by activated alveolar macrophages. Journal of Immunology 140, 2983-2988CrossRefGoogle ScholarPubMed
225Garrido, J.J. et al. (1992) Modulation by neurotensin and neuromedin N of adherence and chemotaxis capacity of murine lymphocytes. Regulatory Peptides 41, 27-37Google ScholarPubMed
226Evers, B.M. et al. (1994) Characterization of functional neurotensin receptors on human lymphocytes. Surgery 116, 134-139; discussion 139–140Google ScholarPubMed
227Hartschuh, W., Weihe, E. and Reinecke, M. (1983) Peptidergic (neurotensin, VIP, substance P) nerve fibres in the skin. Immunohistochemical evidence of an involvement of neuropeptides in nociception, pruritus and inflammation. British Journal of Dermatology 109 Suppl 25, 14-17CrossRefGoogle ScholarPubMed
228Donelan, J. et al. (2006) Corticotropin-releasing hormone induces skin vascular permeability through a neurotensin-dependent process. Proceedings of the National Academy of Sciences of the United States of America 103, 7759-7764CrossRefGoogle ScholarPubMed
229Zhao, D. et al. (2005) Neurotensin stimulates interleukin-8 expression through modulation of I kappa B alpha phosphorylation and p65 transcriptional activity: involvement of protein kinase C alpha. Molecular Pharmacology 67, 2025-2031CrossRefGoogle ScholarPubMed
230Zhao, D. et al. (2003) Neurotensin stimulates IL-8 expression in human colonic epithelial cells through Rho GTPase-mediated NF-kappa B pathways. American Journal of Physiology – Cell Physiology 284, C1397-1404CrossRefGoogle ScholarPubMed
231Brun, P. et al. (2005) Neuropeptide neurotensin stimulates intestinal wound healing following chronic intestinal inflammation. American Journal of Physiology – Gastrointestinal and Liver Physiology 288, G621-629CrossRefGoogle ScholarPubMed
232Martin, S., Vincent, J.P. and Mazella, J. (2003) Involvement of the neurotensin receptor-3 in the neurotensin-induced migration of human microglia. Journal of Neuroscience 23, 1198-1205CrossRefGoogle ScholarPubMed
233Dinh, T.L. and Veves, A. (2006) Treatment of diabetic ulcers. Dermatologic Therapy 19, 348-355CrossRefGoogle ScholarPubMed
234Steed, D.L. et al. (2006) Guidelines for the treatment of diabetic ulcers. Wound Repair and Regeneration 14, 680-692CrossRefGoogle ScholarPubMed
235Pradhan, L., Andersen, N.D., Nabzdyk, C., LoGerfo, F.W. and Veves, A. (2007) Wound healing abnormalities in diabetes and new therapeutic interventions. US Endocrine Disease 2, 68-72CrossRefGoogle Scholar
236Denet, A.R., Vanbever, R. and Preat, V. (2004) Skin electroporation for transdermal and topical delivery. Advanced Drug Delivery Reviews 56, 659-674CrossRefGoogle ScholarPubMed
237Vanbever, R. and Preat, V.V. (1999) In vivo efficacy and safety of skin electroporation Advanced Drug Delivery Reviews 35, 77-88CrossRefGoogle ScholarPubMed
238Lee, P.Y., Chesnoy, S. and Huang, L. (2004) Electroporatic delivery of TGF-beta1 gene works synergistically with electric therapy to enhance diabetic wound healing in db/db mice. Journal of Investigative Dermatology 123, 791-798CrossRefGoogle ScholarPubMed
239Lin, M.P. et al. (2006) Delivery of plasmid DNA expression vector for keratinocyte growth factor-1 using electroporation to improve cutaneous wound healing in a septic rat model. Wound Repair and Regeneration 14, 618-624CrossRefGoogle Scholar
240Gohshi, A. et al. (1998) Changes in adrenocorticotropic hormone (ACTH) release from the cultured anterior pituitary cells of streptozotocin-induced diabetic rats. Biological & Pharmaceutical Bulletin 21, 795-799CrossRefGoogle ScholarPubMed

Further reading, resources and contacts

Blakytny, R. and Jude, E (2006) The molecular biology of chronic wounds and delayed healing in diabetes. Diabetic Medicine 23, 594-608CrossRefGoogle ScholarPubMed
Vinik, A. et al. (2006) Diabetic neuropathies: clinical manifestations and current treatment options. Nature Clinical Practice Endocrinology & Metabolism 2, 269-281CrossRefGoogle ScholarPubMed
Veves, A., Giurini, J.M. and LoGerfo, F.W. (2002) The Diabetic Foot: Medical and Surgical Management, Humana Press, Totowa, NJ, USACrossRefGoogle Scholar
http://diabetes.niddk.nih.gov/dm/pubs/america/contents.htmGoogle Scholar