Cellular factors involved in CXCL8 expression induced by glycated serum albumin in vascular smooth muscle cells.
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.
Choi
Kyung-Ha
KH
Department of Pharmacology, School of Medicine-Pusan National University, Yangsan, Republic of Korea.
Park
Jae-woo
JW
Kim
Hye-Young
HY
Kim
Young-Hee
YH
Kim
Sun-Mi
SM
Son
Yong-Hae
YH
Park
Young-Chul
YC
Eo
Seong-Kug
SK
Kim
Koanhoi
K
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
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