title: Cellular factors involved in CXCL8 expression induced by glycated serum albumin in vascular smooth muscle cells.
abstract: Glycated serum albumin (GSA) promotes vascular complications in diabetes. The aim of this study was to determine if GSA induces chemokine, particularly CXCL8 (IL-8), and to determine intracellular signaling pathways activated by GSA in vascular smooth muscle cells (VSMCs). GSA increased IL-8 transcription via promoter activation and enhanced CXCL8 release from VSMCs. GSA-induced promoter activation of the IL-8 gene was suppressed by dominant-negative mutants of TLR-4, MyD88, and TRIF, but not by a dominant-negative form of TLR-2. In addition, IL-8 up-regulation in response to GSA was inhibited by resveratrol, curcumin, diphenyleneiodium, U0126, and SB202190. Mutation at the NF-kappaB- or C/EBP-binding site, but not at the AP-1-binding site, in the IL-8 promoter region suppressed GSA-induced promoter activation. Moreover, gene delivery of IkappaB suppressed CXCL8 release. This study suggests that GSA induces expression of IL-8 in VSMCs and that TLR-4, mitogen-activated protein kinases, NF-kappaB, and NADPH oxidase are involved in that process.
authors.affiliation: Department of Pharmacology, School of Medicine-Pusan National University, Yangsan, Republic of Korea.
authors.forename: Kyung-Ha
authors.initials: KH
authors.lastname: Choi
authors.forename: Jae-woo
authors.initials: JW
authors.lastname: Park
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Young-Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Sun-Mi
authors.initials: SM
authors.lastname: Kim
authors.forename: Yong-Hae
authors.initials: YH
authors.lastname: Son
authors.forename: Young-Chul
authors.initials: YC
authors.lastname: Park
authors.forename: Seong-Kug
authors.initials: SK
authors.lastname: Eo
authors.forename: Koanhoi
authors.initials: K
authors.lastname: Kim
mesh_terms: D002070:Butadienes / Q000494:pharmacology; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology; D017127:Glycation End Products, Advanced; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D009861:Onium Compounds / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D000077185:Resveratrol; D012709:Serum Albumin / Q000378:metabolism* / Q000494:pharmacology; D013267:Stilbenes / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015533:Transcriptional Activation; D015854:Up-Regulation; D000093423:Glycated Serum Albumin
chemical_list: D002070:Butadienes; C508606:CXCL8 protein, human; D017127:Glycation End Products, Advanced; D016209:Interleukin-8; D016328:NF-kappa B; D009570:Nitriles; D009861:Onium Compounds; D012709:Serum Albumin; D013267:Stilbenes; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C113580:U 0126; C007517:diphenyleneiodonium; D019255:NADPH Oxidases; D020929:Mitogen-Activated Protein Kinase Kinases; D003474:Curcumin; D000077185:Resveratrol; D000093423:Glycated Serum Albumin