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.