Involvement of MAP kinase signal transduction pathway in UVB-induced activation of macrophages in vitro

Ultraviolet B (UVB) radiation causes a variety of biological effects that can be either beneficial or harmful for human health. To exert these effects on a cellular basis, UVB induces a variety of signaling pathways, which act in an independent and additive ways. However, the UVB-induced signal transduction mechanism(s) till date remains not well understood. In the current investigation, we demonstrate p42/44, p38 and JNK MAPK activation in murine peritoneal macrophages on irradiation with UVB as determined by the expression of phospho-p42/44 MAPK, -p38 and -JNK. These responses were found to be rapid and time-dependent, detectable as early as 5 min post UVB irradiation 50 mJ/cm(2) and reached a peak by 15 min. UVB-induced phosphorylation of p42/44, p38 and JNK MAPKs was found to be blocked by Galphai-protein inhibitor, pertussis toxin; tyrosine kinase inhibitor, genistein; and PI3-K inhibitor, wortmannin. The activation of downstream transcription factors, c-jun and c-fos was also observed in response to UVB irradiation. The role of PD98059, SB202190, genistein, and wortmannin in regulating UVB-induced c-jun and c-fos activation and transcription was also investigated. The functional consequences of UVB-induced p42/44 MAPK and p38 MAPK activity were studied using TNF-alpha and NO production in the macrophages. The data suggests the involvement of p42/44, p38 and JNK MAPK pathway and subsequent induction of c-fos and c-jun in the signal transduction process leading to the activation of macrophages exposed to UV13. (C) 2003 Elsevier B.V. All rights reserved.