Heat shock protein-70 mediates the cytoprotective effect of carbon monoxide: Involvement of p38β MAPK and heat shock factor-1

Hong Pyo Kim, Xue Wang, Jinglan Zhang, Gee Young Suh, Ivor J. Benjamin, Stefan W. Ryter, Augustine M.K. Choi

Research output: Contribution to journalArticle

124 Scopus citations

Abstract

Carbon monoxide (CO), a product of heme oxygenase activity, exerts antiapoptotic and anti-inflammatory effects in vitro and in vivo. The anti-inflammatory effects of CO involve the inhibition of TNF-α expression and the enhancement of IL-10 production, resulting in reduced mortality after endotoxin challenge. In this study we demonstrate for the first time that the protective effects of CO involve the increased expression of the 70-kDa inducible heat shock protein (Hsp70) in murine lung endothelial cells and fibroblasts. The p38β MAPK mediated the effects of CO on cytoprotection and Hsp70 regulation. Suppression of Hsp70 expression and/or genetic deletion of heat shock factor-1, the principle transcriptional regulator of Hsp70, attenuated the cytoprotective and immunomodulatory effects of CO in mouse lung cells and in vivo. These data provide a novel mechanism for the protective effects of CO and underscore a potential application of this gaseous molecule in anti-inflammatory therapies.

Original languageEnglish (US)
Pages (from-to)2622-2629
Number of pages8
JournalJournal of Immunology
Volume175
Issue number4
DOIs
StatePublished - Aug 15 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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