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


MeSH Major

  • Carbon Monoxide
  • Cytoprotection
  • DNA-Binding Proteins
  • HSP70 Heat-Shock Proteins
  • Mitogen-Activated Protein Kinase 11
  • Transcription Factors


  • 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-alpha 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 p38beta 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.

publication date

  • August 15, 2005



  • Academic Article



  • eng

PubMed ID

  • 16081837

Additional Document Info

start page

  • 2622

end page

  • 9


  • 175


  • 4