Heat shock protein 70 overexpression affects the response to ultraviolet light in murine fibroblasts. Evidence for increased cell viability and suppression of cytokine release.
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.
Simon
M M
MM
Ludwig Boltzmann Institute of Cell Biology and Immunobiology, Department of Dermatology, University Münster, Germany.
Reikerstorfer
A
A
Schwarz
A
A
Krone
C
C
Luger
T A
TA
Jäättelä
M
M
Schwarz
T
T
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
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