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 UVB.
Sodhi
Ajit
A
School of Biotechnology, Banaras Hindu University, Varanasi 221005, India. ajitsodhi@epatra.com
Sethi
Gautam
G
D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000528:radiation effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014466:Ultraviolet Rays
D004791:Enzyme Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases