title: Effect of heat stress on lipopolysaccharide-induced vascular permeability change in mice.
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 degrees C for 1 h and then returned to 23 degrees 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-alpha (TNF-alpha) and prostaglandin E(2) (PGE(2)) 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-alpha 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-alpha content but not PGE(2) content. These results suggest that heat stress attenuated LPS-induced vascular permeability change by inducing hsp90, leading to inhibition of TNF-alpha production.
authors.affiliation: Department of Pharmacology, Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. taiyo@research.twmu.ac.jp
authors.forename: Taiyo
authors.initials: T
authors.lastname: Suganuma
authors.forename: Kaoru
authors.initials: K
authors.lastname: Irie
authors.forename: Emiko
authors.initials: E
authors.lastname: Fujii
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Yoshioka
authors.forename: Takamura
authors.initials: T
authors.lastname: Muraki
mesh_terms: D000818:Animals; D016227:Benzoquinones; D015153:Blotting, Western; D002199:Capillary Permeability / Q000187:drug effects*; D051546:Cyclooxygenase 2; D015853:Cysteine Proteinase Inhibitors; D015232:Dinoprostone / Q000096:biosynthesis; D005334:Fever / Q000503:physiopathology; D006146:Guanidines; D018882:Heat Stress Disorders / Q000503:physiopathology*; D006360:Heat-Shock Proteins / Q000378:metabolism; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D047029:Lactams, Macrocyclic; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics; D011809:Quinones; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012486:Salmonella typhimurium / Q000737:chemistry; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D016227:Benzoquinones; D015853:Cysteine Proteinase Inhibitors; D006146:Guanidines; D006360:Heat-Shock Proteins; D007527:Isoenzymes; D047029:Lactams, Macrocyclic; D008070:Lipopolysaccharides; D011809:Quinones; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; C037258:gusperimus; C001277:geldanamycin