Cellular factors involved in CXCL8 expression induced by glycated serum albumin in vascular smooth muscle cells

• Published in: Atherosclerosis 2010-03, Vol.209 (1), p.58-65
• Main Authors: Choi, Kyung-Ha, Park, Jae-woo, Kim, Hye-Young, Kim, Young-Hee, Kim, Sun-Mi, Son, Yong-Hae, Park, Young-Chul, Eo, Seong-Kug, Kim, Koanhoi
• Format: Article
• Language: English
• Subjects: Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Blood vessels and receptors; Butadienes - pharmacology; Cardiology. Vascular system; Cardiovascular; Cells, Cultured; Curcumin - pharmacology; CXCL8; Fundamental and applied biological sciences. Psychology; Glycated serum albumin; Humans; Interleukin-8 - genetics; Medical sciences; Mitogen-Activated Protein Kinase Kinases - metabolism; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; NADPH Oxidases - metabolism; NF-kappa B - metabolism; Nitriles - pharmacology; Onium Compounds - pharmacology; Promoter Regions, Genetic; Resveratrol; Serum Albumin - metabolism; Serum Albumin - pharmacology; Stilbenes - pharmacology; Toll-like receptor; Toll-Like Receptor 4 - antagonists & inhibitors; Toll-Like Receptor 4 - metabolism; Transcriptional Activation; Up-Regulation; Vascular smooth muscle cell; Vertebrates: cardiovascular system
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2009.08.030

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-κB- 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 IκB suppressed CXCL8 release. This study suggests that GSA induces expression of IL-8 in VSMCs and that TLR-4, mitogen-activated protein kinases, NF-κB, and NADPH oxidase are involved in that process.