Heat shock inhibits TNF-induced ICAM-1 expression in human endothelial cells via I kappa kinase inhibition

Gary Kohn, Hector R. Wong, Khaled Bshesh, Bin Zhao, Niti Vasi, Alvin Denenberg, Christopher Morris, James Stark, Thomas P. Shanley*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

The pulmonary vascular endothelium plays a critical role in lung inflammation. As a result of proinflammatory cytokine expression, adhesion molecules are upregulated on the surface of the endothelial cells. Adhesion molecules facilitate recruitment of leukocytes and thus, have been targeted for potential anti-inflammatory strategies. Prior induction of the stress response through thermal stimulation, or heat shock, alters proinflammatory gene expression by attenuating NF-κB signaling. As intercellular adhesion molecule-(ICAM) 1 expression is, in part, NF-κB-dependent, we hypothesized that heat shock would inhibit ICAM-1 expression. Heat shocking endothelial cells resulted in heat shock protein (HSP) expression as measured by HSP-70 induction, and decreased TNF-α-induced ICAM-1 expression in a manner that appeared to be transcriptionally mediated. Following heat shock, decreased TNF-α-induced NF-κB activation was observed and was associated with preservation of IκB-α and a decrease in phosphorylated IκB-α that correlated to inhibition of I kappa kinase (IKK) activity. Interestingly, exposing respiratory epithelial cells to heat shock, which results in NF-κB inhibition, did not affect TNF-induced ICAM-1 expression. We conclude that heat shock decreases endothelial cell ICAM-1 expression via inhibition of IKK activity.

Original languageEnglish (US)
Pages (from-to)91-97
Number of pages7
JournalShock
Volume17
Issue number2
DOIs
StatePublished - Feb 2002

Keywords

  • Adhesion molecules
  • Endothelial cells
  • Epithelial cells
  • Heat shock
  • ICAM-1
  • NF-κB
  • TNF-α

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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