Induction of interleukin-8 by ozone is mediated by tyrosine kinase and protein kinase A, but not by protein kinase C.
Ozone is one of the most common air pollutants humans routinely inhale. We have previously shown that in vitro ozone exposure induces the DNA-binding activities of NF-kappaB and NF-IL6 as well as the expression of interleukin 8 in respiratory epithelial cells. In this study, we investigated intracellular signaling steps mediating ozone-induced inflammatory mediator release. A549 cells, a type II like alveolar epithelial cell line, were exposed in vitro to air or 0.1 ppm of ozone in the presence of several kinase inhibitors. Exposure to ozone increased interleukin 8 expression and transcription factor activities in a protein tyrosine kinase (PTK)-dependent and protein kinase A (PKA)-dependent, yet protein kinase C (PKC)-independent, manner. Furthermore, ozone-induced PTK and PKA activities but failed to induce PKC activity. In addition, our results suggest that ozone-induced PTK and PKA activities were reactive oxygen intermediate dependent and occurred in parallel, because specific inhibitors for PTK and PKA failed to block the other kinase's activity. These results indicate that PTK and PKA activities are early events in the signal transduction cascade mediating the ozone-induced activation of NF-kappaB and NF-IL6 as well as the release of interleukin 8.
Department of Environmental Medicine, New York University School of Medicine, Tuxedo 10987, USA.
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Flescher
D002282:Adenocarcinoma, Bronchiolo-Alveolar; D022762:CCAAT-Enhancer-Binding Proteins; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D008175:Lung Neoplasms; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D009687:Nuclear Proteins / Q000187:drug effects / Q000378:metabolism; D010126:Ozone / Q000633:toxicity*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D016209:Interleukin-8; D016328:NF-kappa B; D009687:Nuclear Proteins; D017382:Reactive Oxygen Species; D010126:Ozone; D011505:Protein-Tyrosine Kinases; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C