Autocrine regulation of airway smooth muscle responsiveness.
Bronchial asthma is characterized by airway inflammation, exaggerated airway narrowing to bronchoconstrictor agonists, and attenuated beta-adrenoceptor-mediated airway relaxation. Various cytokines/chemokines have been implicated in the pathogenesis of the airway inflammatory response, and certain cytokines, most notably including specific Th2-type cytokines and IL-1beta, have been shown to directly regulate airway smooth muscle (ASM) responsiveness. Recent evidence supports the concept that the ASM itself has the capacity to endogenously express a number of these cytokines under specific conditions of ASM sensitization. Moreover, these cytokines were found to act in an autocrine manner on the ASM to evoke the 'pro-asthmatic' phenotype of altered airway responsiveness. This cytokine-driven autocrine signaling mechanism in ASM may be triggered by either Fc receptor activation in the atopic (IgE-mediated) sensitized state or by ASM exposure to specific viral respiratory pathogens, most notably including rhinovirus. Furthermore, the autocrine-induced changes in ASM responsiveness are attributed to altered receptor-coupled transmembrane signaling in the sensitized ASM, resulting in perturbed expression and release of second messenger molecules that regulate ASM contraction and relaxation. Collectively, this evidence identifies mechanisms intrinsic to the ASM itself, including autocrine pro-inflammatory signaling and altered receptor/G protein-coupled second messenger activation, that importantly contribute to phenotypic expression of the changes in ASM responsiveness that characterize the asthmatic state.
D000222:Adaptation, Physiological; D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000276:immunology*; D019898:Autocrine Communication / Q000502:physiology*; D001980:Bronchi / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D002648:Child; D016207:Cytokines / Q000502:physiology*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology; D009130:Muscle, Smooth / Q000503:physiopathology*; D014132:Trachea / Q000503:physiopathology
D016207:Cytokines