Protein kinase C‐ε mediates bradykinin‐induced cyclooxygenase‐2 expression in human airway smooth muscle cells
- 18 July 2002
- journal article
- Published by Wiley in The FASEB Journal
- Vol. 16 (11), 1435-1437
- https://doi.org/10.1096/fj.02-0169fje
Abstract
We previously reported that proinflammatory mediator bradykinin (BK) induces cyclooxygenase (COX)-2 expression in human airway smooth muscle (HASM), but the mechanism is unknown in any biological system. Here, we studied the role of specific protein kinase C (PKC) isozyme(s) in COX-2 expression. Among the eight PKC isozymes present in HASM cells, the Ca2+-independent PKC-delta and -epsilon and the Ca2+-dependent PKC-alpha and -betaI were translocated to the nucleus upon BK stimulation. BK-induced COX-2 expression and prostaglandin E2 (PGE2) accumulation were mimicked by the direct PKC activator phorbol 12-myristate 13-acetate (PMA) and inhibited by the broad spectrum PKC inhibitor bisindolylmaleimide I. However, the selective Ca2+-dependent PKC isozyme inhibitor Go 6976 had no effect. Furthermore, the membrane-permeable calcium chelator BAPTA-AM had no effect on BK-induced COX-2 expression and COX activity despite its inhibition of PGE2 accumulation, suggesting the involvement of Ca2+-independent PKC isozymes. Rottlerin, a PKC-delta inhibitor, also had no effect, likely implicating PKC-epsilon. BK-stimulated transcriptional activation of a COX-2 promoter reporter construct was enhanced by overexpression of wild-type PKC-epsilon and abolished by a dominant negative PKC-epsilon, but it was not affected by wild-type or dominant negative PKC-alpha or -delta. Collectively, our results demonstrate that PKC-e mediates BK-induced COX-2 expression in HASM cells.Keywords
Funding Information
- Wellcome Trust (05710)
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