Interleukin-1 beta and rhinovirus sensitize adenylyl cyclase in human airway smooth-muscle cells

Rhinovirus (RV) is a major cause of wheezing in asthmatics and has been rep orted to cause beta (2) adrenergic receptor hyporesponsiveness in human air way smooth muscle (HASM) via cellular secretion of interleukin (IL)-1 beta. We studied the effects of IL-1 beta and RV on cyclic adenosine monophospha te (cAMP) production in HASM cells. Chronic incubation with IL-1 beta or RV caused a significant increase (similar to 3- and similar to 2-fold, respec tively) in forskolin (FSK)-stimulated cAMP production, suggesting a sensiti zation of adenylyl cyclase (AC), The observed augmentation of FSK-stimulate d cAMP formation by IL-1 beta was completely abrogated by pretreatment with an IL-l receptor antagonist or cycloheximide, demonstrating that the effec t is mediated via the IL-1 receptor 1 (IL-1R1) and that de novo protein syn thesis is required. In contrast, RV-induced AC sensitization was not mediat ed via the IL-1R1 but was observed to be protein kinase C-dependent. We sug gest that the sensitization of AC observed after exposure to IL-1 beta or R V infection is a cellular defense mechanism to promote pathways that induce relaxation in the inflamed airway.