Involvement of p53 and interleukin 3 in the up-regulation of CD95 (APO-1/Fas) by X-ray irradiation.
Interleukin 3-dependent bone marrow and Ba/F3 cells present constitutive Fas expression. A dose dependent increase in Fas surface expression was induced in these cells by X-ray irradiation. Using primary cell cultures and established 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 irradiation was negatively modulated by IL-3; an earlier Fas induction was observed 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 expression. X-ray irradiation of Ba/F3 cells induced the expression of functional Fas receptors. Therefore, in IL-3-dependent cells, IL-3 regulates the rate of Fas expression, which is correlated with the degree of apoptosis observed in X-irradiated cells. Finally, we demonstrate that IL-3 controls the degree of Fas expression induced by irradiation through a p53-mediated pathway.
Gutiérrez del Arroyo
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A
Department of Immunology, Centro de Investigaciones Biológicas, CIB-CSIC, Madrid, Spain.
Gil-Lamagniere
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C
Lazaro
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I
de Marco
M C
MC
Layunta
I
I
Silva
A
A
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D007377:Interleukin-3 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013997:Time Factors; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000528:radiation effects*; D019014:fas Receptor / Q000235:genetics*
D007377:Interleukin-3; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor