Extracellular Heat Shock Protein 90 Induces interleukin-8 in Vascular Smooth Muscle Cells

Biochem Biophys Res Commun. 2009 Jan 16;378(3):444-9. doi: 10.1016/j.bbrc.2008.11.063. Epub 2008 Nov 24.

Abstract

Oxidative stress results in sustained release of heat shock protein 90 (HSP90) from vascular smooth muscle cells (VSMCs). The aim of this article is to investigate whether extracellular HSP90 predisposes VSMCs to pro-inflammatory phenotype. Exposure of aortic smooth muscle cells to HSP90 elevated IL-8 release and IL-8 transcript via promoter activation. HSP90-induced IL-8 promoter activation was suppressed by dominant-negative forms of Toll-like receptor (TLR)-4 and MyD88, but not by dominant-negative-forms of TLR-3, TLR-2, and TRIF. IL-8 up-regulation in response to HSP90 was also attenuated by IkappaB, rasveratrol, curcumin, diphenyleneiodium, N-acetylcystein, 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 the promoter activation by HSP90. This study proposes that extracellular HSP90 would contribute to IL-8 elevation in the stressed vasculature, and that TLR-4, mitogen-activated protein kinases, NF-kappaB, and reactive oxygen species are involved in that process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CCAAT-Enhancer-Binding Proteins / metabolism
  • HSP90 Heat-Shock Proteins / metabolism*
  • HSP90 Heat-Shock Proteins / pharmacology
  • Humans
  • Interleukin-8 / genetics*
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism*
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism*
  • NF-kappa B / metabolism
  • Promoter Regions, Genetic / drug effects
  • Reactive Oxygen Species / metabolism
  • Toll-Like Receptor 4 / metabolism
  • Transcription, Genetic
  • Transcriptional Activation*

Substances

  • CCAAT-Enhancer-Binding Proteins
  • HSP90 Heat-Shock Proteins
  • Interleukin-8
  • NF-kappa B
  • Reactive Oxygen Species
  • TLR4 protein, human
  • Toll-Like Receptor 4