Induction of COX-2 by acrolein in rat lung epithelial cells.
Acrolein is a highly reactive alpha, beta-unsaturated aldehyde, and a product of lipid peroxidation reactions. Acrolein is also an environmental pollutant and a key component of cigarette smoke, and has been implicated in multiple respiratory diseases. Lung tissue is a primary target for acrolein toxicity in smokers and may lead to chronic lung inflammation and lung cancer. Chronic inflammation, associated with expression of cyclooxygenase-2 (COX-2) and prostaglandins, are predisposing factors for malignancy. In this study, we investigated the induction of COX-2 by acrolein in rat lung epithelial cells and its related signaling cascade. Induction of COX-2 by acrolein was significant at 6 h post-treatment and was dependent upon NFkappaB activation. The activation of NFkappaB by acrolein was induced as a result of degradation of IkappaBalpha over the time of treatment. In addition, the upstream signaling cascade involved Raf-1/ERK activation by acrolein in the COX-2 induction and was inhibited by GW5074 (a Ras/Raf-1/ERK inhibitor), thereby providing evidence for the role of this cascade in this process. The results of these studies offer an explanation for the mechanism of COX-2 induction by acrolein in rat lung epithelial cells.
Sarkar
Poonam
P
College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 77004, USA.
Hayes
Barbara E
BE
D000171:Acrolein / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D004790:Enzyme Induction; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology* / Q000187:drug effects; D048728:MAP Kinase Kinase Kinase 1 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic; D018631:ras Proteins / Q000378:metabolism
D016328:NF-kappa B; D000171:Acrolein; D051546:Cyclooxygenase 2; D019908:Proto-Oncogene Proteins c-raf; D048049:Extracellular Signal-Regulated MAP Kinases; D048728:MAP Kinase Kinase Kinase 1; D018631:ras Proteins; D002118:Calcium