Involvement of p53 and interleukin 3 in the up-regulation of CD95 (APO-1/Fas) by X-ray irradiation

Interleukin 3-dependent hone marrow and Ba/F3 cells present constitutive Fa s expression. A dose dependent increase in Fas surface expression was induc ed in these cells by X-ray irradiation. Using primary cell cultures and est ablished cell lines derived from p53-null mice (p53(-/-)), we demonstrated that the increase in Fas expression upon X-ray irradiation is dependent on the presence of at least one wild-type p53 allele. Fas induction by X-ray i rradiation was negatively modulated by IL-3; an earlier Fas induction was o bserved in the absence of IL-3 or at low IL-3 concentrations. However, IL-3 withdrawal in non-irradiated cells did not induce an increase in Fas expre ssion. X-ray irradiation of Ba/F3 cells induced the expression of functiona l Fas receptors. Therefore, in IL-3-dependent cells, IL-3 regulates the rat e of Fas expression, which is correlated with the degree of apoptosis obser ved in X-irradiated cells. Finally, we demonstrate that IL-3 controls the d egree of Fas expression induced by irradiation through a p53-mediated pathw ay.