Regulation of human airway mesenchymal cell proliferation by glucocorticoids and beta2-adrenoceptor agonists.
Altered rates of cell proliferation play important roles in the pathogenesis of a variety of conditions, including cancer, inflammation and several airway and cardiovascular diseases. One of the most consistently observed changes in asthmatic airways is an increased volume of airway smooth muscle (ASM), that has been explained by proliferation, hypertrophy, extracellular matrix deposition within the smooth muscle bundles, and more recently, the migration of mesenchymal precursor cells to the airways. The best characterised of these is proliferation of ASM cells. In vitro studies suggest that the proliferation is driven by various mitogens, and ECM proteins found in asthma, such as collagen type I. Therefore, we compared the anti-mitogenic actions of two classes of anti-asthma agents, the glucocorticoids and the beta2-adrenoceptor agonists, in ASM cells grown on collagen type I. Culture on collagen type I prevented the anti-mitogenic actions of glucocorticoids, but not beta2-adrenoceptor agonists. In contrast, glucocorticoids are efficacious in regulating ASM production of GM-CSF, whereas beta2-adrenoceptor agonists are without effect. Therefore, combination therapy may have increased efficacy over glucocorticoids alone in controlling remodelling events due to complementary actions of the two classes of compounds.
Bonacci
John V
JV
Department of Pharmacology, The University of Melbourne, Vic. 3010, Australia.
Stewart
Alastair G
AG
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D000704:Analysis of Variance; D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D005938:Glucocorticoids; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D005346:Fibroblast Growth Factors; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003094:Collagen; D000420:Albuterol