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) ove rexpression on cell viability and on the secretion of UV-inducible imm unological cytokines. Transfected murine fibrosarcoma cells (WEHI-S), overexpressing hsp70 or a sham transfected control were used. Overexpr ession of hsp70 was sufficient to markedly increase cell viability upo n 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 O-2(-) radical s we studied the cell viability upon oxidative stress. Hsp70 overexpre ssion increased viability upon treatment with hydrogen peroxide or men adione, but had no influence on UV-induced O-2(-) 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. H sp70 overexpression markedly decreased the release of IL-6 induced by UVA, UVB and oxidative stress. To test whether the hsp70 mediated supp ression is confined to events caused by UV-light we determined IL-1-me diated effects. IL-1-induced IL-6 release was reduced by hsp70 overexp ression, 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 regulati on of proinflammatory cytokine release induced by UV-exposure.