| Title | Interleukin-1beta and rhinovirus sensitize adenylyl cyclase in human airway smooth-muscle cells. | ||
| Author | Billington, C K; Pascual, R M; Hawkins, M L; Penn, R B; Hall, I P | ||
| Journal | Am J Respir Cell Mol Biol | Publication Year/Month | 2001-May |
| PMID | 11350835 | PMCID | -N/A- |
| Affiliation | 1.Division of Therapeutics & Institute of Cell Signalling, and Public Health Laboratory, University Hospital of Nottingham, Nottingham, United Kingdom. | ||
Rhinovirus (RV) is a major cause of wheezing in asthmatics and has been reported to cause beta2 adrenergic receptor hyporesponsiveness in human airway smooth muscle (HASM) via cellular secretion of interleukin (IL)-1beta. We studied the effects of IL-1beta and RV on cyclic adenosine monophosphate (cAMP) production in HASM cells. Chronic incubation with IL-1beta or RV caused a significant increase (approximately 3- and approximately 2-fold, respectively) in forskolin (FSK)-stimulated cAMP production, suggesting a sensitization of adenylyl cyclase (AC). The observed augmentation of FSK-stimulated cAMP formation by IL-1beta was completely abrogated by pretreatment with an IL-1 receptor antagonist or cycloheximide, demonstrating that the effect is mediated via the IL-1 receptor 1 (IL-1R1) and that de novo protein synthesis is required. In contrast, RV-induced AC sensitization was not mediated via the IL-1R1 but was observed to be protein kinase C-dependent. We suggest that the sensitization of AC observed after exposure to IL-1beta or RV infection is a cellular defense mechanism to promote pathways that induce relaxation in the inflamed airway.