Interleukin-1b Induces Bradykinin B2 Receptor Gene Expression through a Prostanoid Cyclic AMP-Dependent Pathway in Human Bronchial Smooth Muscle Cells

We investigated the hypothesis that inflammatory mediators such as interleukin-1b (IL-1b) might be responsible for the hyperreactivity of asthmatic patients to bradykinin. In cultured human bronchial smooth muscle cells, IL-1b 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 phos-phate formation elicited by bradykinin, indicating its relevance to the contractile response of smooth muscle cells to bradyki-nin. The increase in receptor density was related to an increase in B2 receptor mRNA level corresponding to a 5-fold enhance-ment of the transcriptional rate and to a lengthened half-life of mRNA. These effects of IL-1b were largely inhibited by indo-methacin, suggesting the involvement of a prostanoid pathwa