RT Journal Article SR Electronic T1 Interleukin-1β Induces Bradykinin B2 Receptor Gene Expression through a Prostanoid Cyclic AMP-Dependent Pathway in Human Bronchial Smooth Muscle Cells JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 1009 OP 1015 VO 53 IS 6 A1 Fabien Schmidlin A1 Didier Scherrer A1 Laurent Daeffler A1 Claude Bertrand A1 Yves Landry A1 Jean-Pierre Gies YR 1998 UL http://molpharm.aspetjournals.org/content/53/6/1009.abstract AB We investigated the hypothesis that inflammatory mediators such as interleukin-1β (IL-1β) might be responsible for the hyperreactivity of asthmatic patients to bradykinin. In cultured human bronchial smooth muscle cells, IL-1β elicited a rapid and transient increase in the density of bradykinin B2 receptors without affecting their affinity for ligands. The increase in B2 receptors was correlated to an enhancement of inositol phosphate formation elicited by bradykinin, indicating its relevance to the contractile response of smooth muscle cells to bradykinin. The increase in receptor density was related to an increase in B2 receptor mRNA level corresponding to a 5-fold enhancement of the transcriptional rate and to a lengthened half-life of mRNA. These effects of IL-1β were largely inhibited by indomethacin, suggesting the involvement of a prostanoid pathway in IL-1β transduction process. An increase in prostaglandin E2 levels preceded the mRNA increase, confirming this involvement. Moreover, IL-1β and prostaglandin E2 led to cAMP formation. We propose this predominant transduction pathway of IL-1β to stimulate the transcription of the bradykinin B2 gene in human bronchial smooth muscle cells as a major mechanism involved in the hyperresponsiveness of asthmatic patients to bradykinin. The American Society for Pharmacology and Experimental Therapeutics