title: Interleukin-6 induces thermotolerance in cultured Caco-2 cells independent of the heat shock response.
abstract: In recent studies, induction of the heat shock response increased IL-6 production in gut mucosa in vivo and in cultured Caco-2 cells in vitro. The heat shock response is associated with increased survival of cells exposed to otherwise lethal hyperthermia, so called thermotolerance, but the role of IL-6 in the induction of thermotolerance is not known. We tested the hypothesis that treatment of cultured Caco-2 cells with IL-6 results in the development of thermotolerance. Cells were treated with human recombinant IL-6 for 1h followed by 3 h recovery in cytokine-free medium whereafter cells were exposed to heat stress (48 degrees C for 2 h). In untreated cells, the heat stress resulted in an approximately 80% cell death. In cells treated with IL-6, cell viability after heat stress was significantly improved and was doubled at an IL-6 concentration of 20 ng/ml. Treatment of the cells with other cytokines (IL-4, IL-10, IL-1beta, or TNFalpha) did not induce thermotolerance, suggesting that the effect of IL-6 may be specific for this cytokine. The induction of thermotolerance by IL-6 was blocked by an IL-6 receptor antibody, suggesting that the development of thermotolerance was receptor-mediated. Treatment of cells with IL-6 did not induce an heat shock response as suggested by unaltered heat shock protein 70 and 90 levels and unaffected heat shock factor DNA binding activity. In addition, the IL-6-induced thermotolerance was not inhibited by quercetin. The present study provides the first evidence of IL-6-induced thermotolerance and suggests that this effect of IL-6 is independent of the heat shock response.
authors.affiliation: Department of Surgery, University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Dan D
authors.initials: DD
authors.lastname: Hershko
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Robb
authors.forename: Guang-ju
authors.initials: GJ
authors.lastname: Luo
authors.forename: James H
authors.initials: JH
authors.lastname: Paxton
authors.forename: Per-Olof
authors.initials: PO
authors.lastname: Hasselgren
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018938:Caco-2 Cells; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases; D016207:Cytokines / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D020895:Enterocytes / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D018841:HSP90 Heat-Shock Proteins / Q000096:biosynthesis; D006358:Hot Temperature; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D007976:Leupeptins / Q000494:pharmacology; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors; D046988:Proteasome Endopeptidase Complex; D013696:Temperature; D013997:Time Factors; D014162:Transfection
chemical_list: D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D015850:Interleukin-6; D007976:Leupeptins; D009097:Multienzyme Complexes; D004247:DNA; D008156:Luciferases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde