Benzo[a]pyrene diol epoxide up-regulates COX-2 expression through NF-kappaB in rat astrocytes.
Cyclooxygenase may be important in the pathogenesis of smoking-related cancer because it activates carcinogens and is highly inducible in inflammation. Benzo[a]pyrene (B[a]P) is one of the most common ingredients of cigarette smoke and benzo[a]pyrene diol epoxide (BPDE) is a metabolic product of B[a]P. Cigarette smoking-induced inflammation has been found in several tissues and in association with cyclooxygenase-2 (COX-2) expression. The contribution of COX-2 to peripheral inflammation is well documented, however, little is known about its role in brain inflammation. We studied COX-2 expression following treatment with BPDE in the cortical cells of Sprague-Dawley rats in vivo, as well as in DI TNC1 rat astrocytes and rat pheochromocytoma PC-12 cells (neurons) cultured in vitro. Our data showed that BPDE increases levels of COX-2 mRNA and protein in cortical cells of Sprague-Dawley rats. BPDE also increases levels of COX-2 mRNA in PC-12 and DI TNC1 cells. Induction of COX-2 protein was only found in DI TNC1 cells. Gel shift assay and western blot revealed increased NF-kappaB binding activity and protein level after treatment with BPDE. Experiments were performed to define the signaling mechanism by which BPDE induces COX-2, and suggested that BPDE-mediated COX-2 induction increases the risk of brain inflammation.
Weng
Mao-Wen
MW
Institute of Toxicology, Chung Shan Medical University, 110, Sector 1, Chien-Kuo N. Road, Taichung 40203, Taiwan, ROC.
Hsiao
Yi-Min
YM
Chen
Chun-Jung
CJ
Wang
Jih-Pyang
JP
Chen
Wen-Chi
WC
Ko
Jiunn-Liang
JL
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002273:Carcinogens / Q000633:toxicity*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002273:Carcinogens; D007527:Isoenzymes; D016328:NF-kappa B; D012333:RNA, Messenger; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases