The induction of cyclo-oxygenase-2 in human pulmonary epithelial cell culture (A549) activated by IL-1beta is inhibited by tyrosine kinase inhibitors.
Cyclo-oxygenase (COX) exists as two isoforms. In endothelial cells, the induction of COX (COX-2) elicited by endotoxin or inflammatory cytokines is mediated by tyrosine kinase. Here we have investigated whether the induction of COX-2 elicited by IL-1beta in human pulmonary epithelial cells (A549) is mediated by tyrosine kinase. The activity of COX-2 was assessed by measuring the accumulation of PGE2 by radioimmunoassay. The expression of COX-2 protein was detected by immunoblot using specific antibodies to COX-2. Untreated A549 cells contained no COX-2 protein and released low levels of PGE2 (<0.3 ng/ml for 24h). A549 cells treated with IL-1beta (0.01 to 10 ng/ml) contained COX-2 protein and released greater amounts of PGE2. The increased COX-2 protein and activity in response to IL-1beta (10 ng/ml) was inhibited by the tyrosine kinase inhibitors tyrphostin (AG126; 0.015 to 15 microM) or erbstatin (0.004 to 4 microM). Thus, the induction of COX-2 by IL-1beta in epithelial cells is mediated by tyrosine kinase.
Akarasereenont
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The William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London EC1M 6BQ, United Kingdom.
Thiemermann
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C
D002460:Cell Line; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D007527:Isoenzymes / Q000096:biosynthesis*; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004791:Enzyme Inhibitors; D006873:Hydroquinones; D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D011505:Protein-Tyrosine Kinases; D015232:Dinoprostone; C048212:erbstatin