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Abstract
The role of Fas/Fas ligand in ultraviolet B (UVB)-induced apoptosis of murine peritoneal macrophages, the terminally differentiated, non-dividing cells was investigated. UVB (100 mJ/cm2) irradiation induced apoptosis in macrophages concurrent with expression of Fas, Fas ligand, Fas-associated death domain (FADD), activation of caspase-8, -3 and cleavage of poly (ADP-ribose) polymerase (PARP). Pretreatment of macrophages with a p38 mitogen activated protein kinase (MAPK) inhibitor SB202190, and c-Jun N-terminal kinase (JNK) inhibitor SP600125, inhibited UVB irradiation induced Fas expression and apoptosis. Alternatively, pretreatment with MAP kinase kinase (MEK) inhibitor PD98059, and phosphatidylinositol 3-kinase (PI3-K) inhibitor wortmannin, enhanced UVB induced expression of Fas and apoptosis. Apoptosis-inducing factor (AIF) release from mitochondria and Bcl-2 downregulation is also observed during apoptosis in UVB-irradiated macrophages. The data suggests that UVB-induced apoptosis is at least in part mediated by Fas/FasL system, and that MAPKs and PI3-K play an important role in the apoptotic process of macrophages exposed to UVB irradiation.
This work has been supported by grants from Department of Biotechnology, Government of India, and University Grants Commission, New Delhi to Prof. A. Sodhi. Gautam Sethi is a recipient of CSIR-SRF.