Airway wall remodelling and hyperresponsiveness: modelling remodelling in vitro and in vivo.
Airway wall remodelling contributes to the airway hyperresponsiveness that characterizes asthma. An increase in airway smooth muscle (ASM) volume is quantitatively important in the overall remodelling response and may be considered as a target for new therapeutic approaches to chronic asthma. ASM volume increases result from both hypertrophic as well as hyperplastic growth, the latter having been more extensively investigated. There are relatively few in vivo models available for analysis of the underlying mechanism(s) or their regulation by drugs. Human ASM in culture has been used to investigate potential stimuli for ASM proliferation and the signal transduction pathways that subserve these responses. The mitogen-activated protein kinase (MAPK) family members, ERK 1/2 and the phosphoinositol-3-kinase (PI3K) pathways each contribute to the signalling of G1 progression/S-phase entry in ASM. Glucocorticoids and beta(2)-adrenoceptor agonists attenuate, but do not prevent proliferative responses of ASM. Thus, there is scope for improved pharmacological control of this chronic and progressive aspect of asthma pathogenesis.
Stewart
A G
AG
Department of Pharmacology, University of Melbourne, Victoria 3010, Australia. astew@clyde.its.unimelb.edu.au
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D001249:Asthma / Q000503:physiopathology*; D001696:Biomechanical Phenomena; D018929:Cell Culture Techniques; D002453:Cell Cycle; D002455:Cell Division; D016207:Cytokines / Q000494:pharmacology; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D006965:Hyperplasia; D006984:Hypertrophy; D007249:Inflammation; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008934:Mitogens; D008954:Models, Biological; D009130:Muscle, Smooth / Q000033:anatomy & histology* / Q000473:pathology; D012137:Respiratory System / Q000033:anatomy & histology* / Q000473:pathology; D015398:Signal Transduction
D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D016207:Cytokines; D005938:Glucocorticoids; D006133:Growth Substances; D008934:Mitogens; D020928:Mitogen-Activated Protein Kinases