Granulocyte-macrophage colony-stimulating factor enhances wound healing in diabetes via upregulation of proinflammatory cytokines

Summary Background  Chronic ulceration, especially in diabetes, remains a substantial clinical problem. Exogenous granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) is efficacious in the treatment of chronic wound healing in both animal models and patients, but its role in diabetic wounds rem...

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Veröffentlicht in:British journal of dermatology (1951) 2010-03, Vol.162 (3), p.478-486
Hauptverfasser: Fang, Y., Shen, J., Yao, M., Beagley, K.W., Hambly, B.D., Bao, S.
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container_end_page 486
container_issue 3
container_start_page 478
container_title British journal of dermatology (1951)
container_volume 162
creator Fang, Y.
Shen, J.
Yao, M.
Beagley, K.W.
Hambly, B.D.
Bao, S.
description Summary Background  Chronic ulceration, especially in diabetes, remains a substantial clinical problem. Exogenous granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) is efficacious in the treatment of chronic wound healing in both animal models and patients, but its role in diabetic wounds remains to be explored. Objectives  Using a diabetic mouse model, to investigate the role of GM‐CSF in wound healing. Methods  Clinical observation, histopathology, immunohistochemistry and cytokine assays. Results  There was a significant reduction (50%) in GM‐CSF production in the wounds of the diabetics compared with nondiabetics. Exogenous GM‐CSF substantially enhanced the wound healing in diabetic mice, accompanied by increased interleukin‐6 and monocyte chemoattractant protein‐1 production. The elevated cytokines correlated with increased neovascularization, and infiltration of macrophages and neutrophils. GM‐CSF showed no beneficial effects in nondiabetic wound healing. Conclusions  Our results provide useful guidelines for the clinical management of chronic ulceration in diabetes.
doi_str_mv 10.1111/j.1365-2133.2009.09528.x
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Exogenous granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) is efficacious in the treatment of chronic wound healing in both animal models and patients, but its role in diabetic wounds remains to be explored. Objectives  Using a diabetic mouse model, to investigate the role of GM‐CSF in wound healing. Methods  Clinical observation, histopathology, immunohistochemistry and cytokine assays. Results  There was a significant reduction (50%) in GM‐CSF production in the wounds of the diabetics compared with nondiabetics. Exogenous GM‐CSF substantially enhanced the wound healing in diabetic mice, accompanied by increased interleukin‐6 and monocyte chemoattractant protein‐1 production. The elevated cytokines correlated with increased neovascularization, and infiltration of macrophages and neutrophils. GM‐CSF showed no beneficial effects in nondiabetic wound healing. Conclusions  Our results provide useful guidelines for the clinical management of chronic ulceration in diabetes.</description><identifier>ISSN: 0007-0963</identifier><identifier>EISSN: 1365-2133</identifier><identifier>DOI: 10.1111/j.1365-2133.2009.09528.x</identifier><identifier>PMID: 19799605</identifier><identifier>CODEN: BJDEAZ</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Analysis of Variance ; Animals ; Biological and medical sciences ; Chemokine CCL2 - biosynthesis ; Collagen - metabolism ; Colony-Stimulating Factors - metabolism ; cytokines ; Cytokines - metabolism ; Dermatology ; diabetes ; Diabetes Mellitus, Experimental - metabolism ; Diabetes. Impaired glucose tolerance ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Female ; granulocyte-macrophage colony-stimulating factor ; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism ; Interleukin-6 - biosynthesis ; Male ; Medical sciences ; Mice ; Mice, Knockout ; Models, Animal ; Neovascularization, Physiologic - physiology ; proinflammatory wound healing ; Up-Regulation - physiology ; Wound Healing - physiology</subject><ispartof>British journal of dermatology (1951), 2010-03, Vol.162 (3), p.478-486</ispartof><rights>2009 The Authors. 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Exogenous granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) is efficacious in the treatment of chronic wound healing in both animal models and patients, but its role in diabetic wounds remains to be explored. Objectives  Using a diabetic mouse model, to investigate the role of GM‐CSF in wound healing. Methods  Clinical observation, histopathology, immunohistochemistry and cytokine assays. Results  There was a significant reduction (50%) in GM‐CSF production in the wounds of the diabetics compared with nondiabetics. Exogenous GM‐CSF substantially enhanced the wound healing in diabetic mice, accompanied by increased interleukin‐6 and monocyte chemoattractant protein‐1 production. The elevated cytokines correlated with increased neovascularization, and infiltration of macrophages and neutrophils. GM‐CSF showed no beneficial effects in nondiabetic wound healing. Conclusions  Our results provide useful guidelines for the clinical management of chronic ulceration in diabetes.</description><subject>Analysis of Variance</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Chemokine CCL2 - biosynthesis</subject><subject>Collagen - metabolism</subject><subject>Colony-Stimulating Factors - metabolism</subject><subject>cytokines</subject><subject>Cytokines - metabolism</subject><subject>Dermatology</subject><subject>diabetes</subject><subject>Diabetes Mellitus, Experimental - metabolism</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>Female</subject><subject>granulocyte-macrophage colony-stimulating factor</subject><subject>Granulocyte-Macrophage Colony-Stimulating Factor - metabolism</subject><subject>Interleukin-6 - biosynthesis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Models, Animal</subject><subject>Neovascularization, Physiologic - physiology</subject><subject>proinflammatory wound healing</subject><subject>Up-Regulation - physiology</subject><subject>Wound Healing - physiology</subject><issn>0007-0963</issn><issn>1365-2133</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU-P0zAQxSMEYsvCV0C-AKcEO07s5MCBXaCAViAt_47WxBm37iZ2iRO2PfLNcbal3PDFlub3ZjzvJQlhNGPxvNxkjIsyzRnnWU5pndG6zKtsdy9ZnAr3kwWlVKa0FvwseRTChlLGaUkfJmeslnUtaLlIfi8HcFPn9X7EtAc9-O0aVki077zbp2G0_dTBaN2KGNCjHwi6NTiNgdz6ybVkjdDNVetIa6HBMVZ-WSDTdsDVndQ74g3ZDt4600HfQ-yyJ3Ggv7EOw-PkgYEu4JPjfZ58e_f26-X79Orz8sPl66tUF1VRpbJosJLMgECT50gLbBmXRiMvJIhaSFpzZgzSsm2aVgvBJJTIoEaqOTUNP09eHPrGn_ycMIyqt0Fj14FDPwUlOa9EIYSM5PP_kjkro-dFFcGnR3BqemzVdrA9DHv1194IPDsCEDR0JnqtbThxeV7SiM3cqwN3azvc_-tD1Ry32qg5VTWnqua41V3caqcuPr6ZX1GfHvQ2jLg76WG4UXEfWaofn5Yq7vb9-uJLra75H6QUsE8</recordid><startdate>201003</startdate><enddate>201003</enddate><creator>Fang, Y.</creator><creator>Shen, J.</creator><creator>Yao, M.</creator><creator>Beagley, K.W.</creator><creator>Hambly, B.D.</creator><creator>Bao, S.</creator><general>Blackwell Publishing Ltd</general><general>Wiley-Blackwell</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>201003</creationdate><title>Granulocyte-macrophage colony-stimulating factor enhances wound healing in diabetes via upregulation of proinflammatory cytokines</title><author>Fang, Y. ; Shen, J. ; Yao, M. ; Beagley, K.W. ; Hambly, B.D. ; Bao, S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4848-74be871fa6ef22e04ed137fce347a69670931ffe05dbbdc6617a5e1a9e0c30fb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Analysis of Variance</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Chemokine CCL2 - biosynthesis</topic><topic>Collagen - metabolism</topic><topic>Colony-Stimulating Factors - metabolism</topic><topic>cytokines</topic><topic>Cytokines - metabolism</topic><topic>Dermatology</topic><topic>diabetes</topic><topic>Diabetes Mellitus, Experimental - metabolism</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>Female</topic><topic>granulocyte-macrophage colony-stimulating factor</topic><topic>Granulocyte-Macrophage Colony-Stimulating Factor - metabolism</topic><topic>Interleukin-6 - biosynthesis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Models, Animal</topic><topic>Neovascularization, Physiologic - physiology</topic><topic>proinflammatory wound healing</topic><topic>Up-Regulation - physiology</topic><topic>Wound Healing - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fang, Y.</creatorcontrib><creatorcontrib>Shen, J.</creatorcontrib><creatorcontrib>Yao, M.</creatorcontrib><creatorcontrib>Beagley, K.W.</creatorcontrib><creatorcontrib>Hambly, B.D.</creatorcontrib><creatorcontrib>Bao, S.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>British journal of dermatology (1951)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fang, Y.</au><au>Shen, J.</au><au>Yao, M.</au><au>Beagley, K.W.</au><au>Hambly, B.D.</au><au>Bao, S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Granulocyte-macrophage colony-stimulating factor enhances wound healing in diabetes via upregulation of proinflammatory cytokines</atitle><jtitle>British journal of dermatology (1951)</jtitle><addtitle>Br J Dermatol</addtitle><date>2010-03</date><risdate>2010</risdate><volume>162</volume><issue>3</issue><spage>478</spage><epage>486</epage><pages>478-486</pages><issn>0007-0963</issn><eissn>1365-2133</eissn><coden>BJDEAZ</coden><abstract>Summary Background  Chronic ulceration, especially in diabetes, remains a substantial clinical problem. Exogenous granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) is efficacious in the treatment of chronic wound healing in both animal models and patients, but its role in diabetic wounds remains to be explored. Objectives  Using a diabetic mouse model, to investigate the role of GM‐CSF in wound healing. Methods  Clinical observation, histopathology, immunohistochemistry and cytokine assays. Results  There was a significant reduction (50%) in GM‐CSF production in the wounds of the diabetics compared with nondiabetics. Exogenous GM‐CSF substantially enhanced the wound healing in diabetic mice, accompanied by increased interleukin‐6 and monocyte chemoattractant protein‐1 production. The elevated cytokines correlated with increased neovascularization, and infiltration of macrophages and neutrophils. GM‐CSF showed no beneficial effects in nondiabetic wound healing. Conclusions  Our results provide useful guidelines for the clinical management of chronic ulceration in diabetes.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>19799605</pmid><doi>10.1111/j.1365-2133.2009.09528.x</doi><tpages>9</tpages></addata></record>
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ispartof British journal of dermatology (1951), 2010-03, Vol.162 (3), p.478-486
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source Oxford University Press Journals All Titles (1996-Current); MEDLINE; Wiley Online Library Journals Frontfile Complete
subjects Analysis of Variance
Animals
Biological and medical sciences
Chemokine CCL2 - biosynthesis
Collagen - metabolism
Colony-Stimulating Factors - metabolism
cytokines
Cytokines - metabolism
Dermatology
diabetes
Diabetes Mellitus, Experimental - metabolism
Diabetes. Impaired glucose tolerance
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Female
granulocyte-macrophage colony-stimulating factor
Granulocyte-Macrophage Colony-Stimulating Factor - metabolism
Interleukin-6 - biosynthesis
Male
Medical sciences
Mice
Mice, Knockout
Models, Animal
Neovascularization, Physiologic - physiology
proinflammatory wound healing
Up-Regulation - physiology
Wound Healing - physiology
title Granulocyte-macrophage colony-stimulating factor enhances wound healing in diabetes via upregulation of proinflammatory cytokines
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