Effect of Heat Stress on Lipopolysaccharide-Induced Vascular Permeability Change in Mice
- Taiyo Suganuma, Ph.D., Department of Pharmacology, Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. E-mail:taiyo{at}research.twmu.ac.jp
Abstract
The effect of heat shock protein (hsp) induction on lipopolysaccharide (LPS)-induced increase in vascular permeability was studied in mice as a model of inflammatory mediator-induced inflammatory response. Mice were exposed to an ambient temperature of 43°C for 1 h and then returned to 23°C to recover up to 24 h. Dermal contents of hsp70 and hsp90 but not heat shock cognate protein (hsc)70 increased at 6 h after heat exposure and returned to the basal level at 24 h. LPS was injected subcutaneously at 0, 2, 4, 6, or 24 h after heat exposure. Two hours after LPS injection, vascular permeability was assessed by dermal accumulation of intravenously injected dye. LPS-induced dye leakage was reduced by 42 and 49% in heat-exposed mice after recovery for 4 and 6 h, respectively. Increases in dermal tumor necrosis factor-α (TNF-α) and prostaglandin E2 (PGE2) contents induced by LPS were significantly reduced in the heat-stressed mice recovered for 6 h. LPS-induced increase in cyclooxygenase-2 but not TNF-α mRNA was attenuated in heat-stressed mice. Deoxyspergualin, an inhibitor of hsc70 and hsp90, and geldanamycin, a specific hsp90 inhibitor, dose dependently reversed the inhibitory effect of heat stress on LPS-induced dye leakage and dermal TNF-α content but not PGE2 content. These results suggest that heat stress attenuated LPS-induced vascular permeability change by inducing hsp90, leading to inhibition of TNF-α production.
Footnotes
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This work was partly supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture, Japan (No. 11672279 and No. 12672159).
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DOI: 10.1124/jpet.102.035758
- Abbreviations:
- hsp
- heat shock protein
- LPS
- lipopolysaccharide
- hsc
- heat shock cognate protein
- TNF-α
- tumor necrosis factor α
- PGE2
- prostaglandin E2
- DSG
- deoxyspergualin
- GA
- geldanamycin
- PSB
- pontamine sky blue
- PBS
- phosphate-buffered saline
- RT-PCR
- reverse transcriptase-polymerase chain reaction
- COX-2
- cyclooxygenase-2
- NF-κB
- nuclear factor κB
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- Received March 11, 2002.
- Accepted August 7, 2002.
- The American Society for Pharmacology and Experimental Therapeutics
