title: Heat shock protein 70 overexpression affects the response to ultraviolet light in murine fibroblasts. Evidence for increased cell viability and suppression of cytokine release.
abstract: To elucidate cellular concepts for protection against ultraviolet (UV) light we investigated the effect of heat shock protein 70 (hsp70) overexpression on cell viability and on the secretion of UV-inducible immunological cytokines. Transfected murine fibrosarcoma cells (WEHI-S), overexpressing hsp70 or a sham transfected control were used. Overexpression of hsp70 was sufficient to markedly increase cell viability upon treatment with UVB (290-320 nm). Since long wave UV (UVA, 320-400 nm) as well as UVB turned out to stimulate the release of O2- radicals we studied the cell viability upon oxidative stress. Hsp70 overexpression increased viability upon treatment with hydrogen peroxide or menadione, but had no influence on UV-induced O2- release. UV-light is known to upregulate immunologic and proinflammatory cytokines such as IL-1 and IL-6. Oxidative stress appeared to exert a similar effect. Hsp70 overexpression markedly decreased the release of IL-6 induced by UVA, UVB and oxidative stress. To test whether the hsp70 mediated suppression is confined to events caused by UV-light we determined IL-1-mediated effects. IL-1-induced IL-6 release was reduced by hsp70 overexpression, whereas the IL-1 mediated activation of nuclear factor kappa B was not affected. Our data suggests that hsp70 plays a central role not only in cell protection against UV-light, but also in the regulation of proinflammatory cytokine release induced by UV-exposure.
authors.affiliation: Ludwig Boltzmann Institute of Cell Biology and Immunobiology, Department of Dermatology, University Münster, Germany.
authors.forename: M M
authors.initials: MM
authors.lastname: Simon
authors.forename: A
authors.initials: A
authors.lastname: Reikerstorfer
authors.forename: A
authors.initials: A
authors.lastname: Schwarz
authors.forename: C
authors.initials: C
authors.lastname: Krone
authors.forename: T A
authors.initials: TA
authors.lastname: Luger
authors.forename: M
authors.initials: M
authors.lastname: Jäättelä
authors.forename: T
authors.initials: T
authors.lastname: Schwarz
mesh_terms: D000818:Animals; D001483:Base Sequence; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D011836:Radiation Tolerance / Q000502:physiology*; D011837:Radiation-Protective Agents / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays / Q000009:adverse effects*; D014812:Vitamin K / Q000494:pharmacology
chemical_list: D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; D016328:NF-kappa B; D011837:Radiation-Protective Agents; D011994:Recombinant Proteins; D013481:Superoxides; D014812:Vitamin K; D006861:Hydrogen Peroxide