Keratinocyte apoptosis induced by ultraviolet B radiation and CD95 ligation - Differential protection through epidermal growth factor receptor activation and Bcl-x(L) expression

Previous work has shown that activation of the epidermal growth factor rece ptor by endogenous or exogenous signals markedly enhances survival of cultu red keratinocytes upon cellular stress such as passaging. This is due, in p art, to epidermal-growth-factor-receptor-dependent expression of Bcl-x(L), an antiapoptotic Bcl-2 homolog. In this study we tested whether epidermal-g rowth-factor-receptor-dependent signal transduction and attendant Bcl-x(L) expression affected survival of human keratinocytes upon exposure to a freq uently encountered apoptotic stimulus, radiation with ultraviolet B. We des cribe that blocking epidermal-growth-factor-receptor-dependent signal trans duction sensitized normal keratinocytes to undergo apoptosis upon ultraviol et B radiation with solar light characteristics. Forced expression of Bcl-x (L) partially but significantly inhibited ultraviolet-B-induced apoptosis o f immortalized keratinocytes (HaCaT). Bcl-x(L) overexpression afforded no p rotection to HaCaT cells against apoptosis induced by binding of an agonist antibody to the death receptor CD95, however. CD95 activation has previous ly been shown to functionally contribute to apoptosis in ultraviolet-irradi ated keratinocytes. These results indicate that epidermal growth factor rec eptor activation and attendant Bcl-x(L) expression provided a physiological ly relevant protective pathway of keratinocytes against ultraviolet-induced but not CD95-dependent apoptosis.