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Heat shock protein-70 mediates the cytoprotective effect of carbon monoxide: involvement of p38 beta MAPK and heat shock factor-1. J Immunol 2005 Aug 15;175(4):2622-9

Date

08/06/2005

Pubmed ID

16081837

DOI

10.4049/jimmunol.175.4.2622

Scopus ID

2-s2.0-23444437384   122 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-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.

Author List

Kim HP, Wang X, Zhang J, Suh GY, Benjamin IJ, Ryter SW, Choi AM

Author

Ivor J. Benjamin MD Center Director, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Active Transport, Cell Nucleus
Animals
Apoptosis
Carbon Monoxide
Cells, Cultured
Cytoprotection
DNA-Binding Proteins
Endothelial Cells
Enzyme Activation
Female
Fibroblasts
HSP70 Heat-Shock Proteins
Heat Shock Transcription Factors
Lipopolysaccharides
Lung
Male
Mice
Mice, Inbred BALB C
Mice, Knockout
Mitogen-Activated Protein Kinase 11
Shock, Septic
Survival Rate
Transcription Factors
Tumor Necrosis Factor-alpha
Up-Regulation
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a