The role of reactive nitrogen species and cigarette smoke in activation of transcription factor NF-kappaB and implication to inflammatory processes.
Using the electromobility shift assay (EMSA) in the rat myoblast system, the activation of transcription factor NF-kappaB by reactive nitrogen species was evaluated. Two distinct patterns of activation were demonstrated. Whereas NO donor, SNAP, activated NF-kappaB in the classical pathway, which led to a transient response, NF-kappaB activation by peroxynitrite donor, SIN-1, was mediated by an alternative pathway, which has been demonstrated in previous works to involve tyrosine nitration of the NF-kappaB inhibitory protein I-kappaB alpha. This led to a constitutive non-transient activation of NF-kappaB and a prolonged inflammatory reaction. Lymphocytes exposed to mild intensity of cigarette smoke for 8 h, which activated NF-kappaB, exhibited a decrease in the fraction of apoptotic cells from 27% to 19% compared with lymphocytes exposed to atmospheric air, using the FACS Annexin V assay. This also has been shown in previous works to be mediated by peroxynitrite. Thus, mild exposure to cigarette smoke induces NF-kappaB activation, which can attenuate apoptosis in human lymphocytes and lead to prolonged inflammatory response. A possible proposed mechanism for induction of chronic inflammatory response may involve peroxynitrite-induced activation of NF-kappaB.
Bar-Shai
M
M
Department of Anatomy and Cell Biology, Rappaport Faculty of Medicine, Technion-Israel Institution of Technology, Haifa, Israel.
Hasnis
E
E
Wiener-Megnazi
Z
Z
Reznick
A Z
AZ
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D030421:Peroxynitrous Acid / Q000378:metabolism*; D051381:Rats; D012906:Smoke; D014026:Nicotiana
D016328:NF-kappa B; D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; D012906:Smoke; D030421:Peroxynitrous Acid; C002385:linsidomine; D008981:Molsidomine; D010396:Penicillamine