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http://dx.doi.org/10.5352/JLS.2008.18.12.1637

Roles of TLR-4 and NF-κB in Interleukin-6 Expression Induced by Heat Shock Protein 90 in Vascular Smooth Muscle Cells  

Rhim, Byung-Yong (Department of Pharmacology, School of Medicine - Pusan National University)
Kim, Kang-Seong (Department of Pharmacology, School of Medicine - Pusan National University)
Kim, Koan-Hoi (Department of Pharmacology, School of Medicine - Pusan National University)
Publication Information
Journal of Life Science / v.18, no.12, 2008 , pp. 1637-1643 More about this Journal
Abstract
This study has investigated whether extracellular HSP90 predisposes vascular smooth muscle cells (VSMCs) to pro-inflammatory phenotype. Exposure of rat aortic smooth muscle cells to HSP90 not only enhanced IL-6 release but also profoundly induced IL-6 transcript via promoter activation. HSP90-induced IL-6 promoter activation was suppressed by dominant-negative forms of Toll-like receptor (TLR)-4 and myeloid differentiation factor 88 (MyD88), but not by dominant-negative-forms of TLR-3 and TIR-domain-containing adapter-inducing interferon-${\beta}$ (TRIF). Curcumin, which inhibits dimerization of TLR-4, also attenuated the IL-6 induction by HSP90. Mutation at the NF-${\kappa}B$- or C/EBP-binding site in the IL-6 promoter region suppressed the promoter activation in response to HSP90. The gene delivery of $I{\kappa}B$ using recombinant adenoviruses and treatment with resveratrol, which inhibit NF-${\kappa}B$ activity, attenuated the HSP90-induced IL-6 release from VSMCs. The present study proposes that extracellular HSP90 would contribute to inflammatory reaction in the stressed vasculature by inducing IL-6 in VSMCs, and that TLR-4 and NF-${\kappa}B$ would play active roles in the process.
Keywords
Interleukin 8; heat shock protein 90; toll-like receptor; vascular smooth muscle cell;
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