TY - JOUR T1 - Interleukin-1β Induces Bradykinin B<sub>2</sub> Receptor Gene Expression through a Prostanoid Cyclic AMP-Dependent Pathway in Human Bronchial Smooth Muscle Cells JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1009 LP - 1015 VL - 53 IS - 6 AU - Fabien Schmidlin AU - Didier Scherrer AU - Laurent Daeffler AU - Claude Bertrand AU - Yves Landry AU - Jean-Pierre Gies Y1 - 1998/06/01 UR - http://molpharm.aspetjournals.org/content/53/6/1009.abstract N2 - 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 ER -