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Glucocorticoids reduce the levels of the proinflammatory and fibrogenic cytokine, granulocyte\u2010macrophage colony\u2010stimulating factor (GM\u2010CSF) produced by human cultured airway smooth muscle (ASM). We have contrasted the effects of a synthetic glucocorticoid, dexamethasone, on thrombin\u2010 and IL\u20101<jats:italic>\u03b1<\/jats:italic>\u2010stimulated GM\u2010CSF production in human ASM cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Although IL\u20101<jats:italic>\u03b1<\/jats:italic> stimulated three\u2010fold higher levels of GM\u2010CSF mRNA and protein compared to thrombin, dexamethasone concentration\u2010dependently reduced IL\u20101<jats:italic>\u03b1<\/jats:italic>\u2010stimulated GM\u2010CSF more potently and to a greater extent than the response to thrombin. This pattern of glucocorticoid regulation was also observed at the GM\u2010CSF mRNA level and was reproduced with other glucocorticoids such as fluticasone propionate.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>IL\u20101<jats:italic>\u03b1<\/jats:italic> and thrombin stimulated NF\u2010<jats:italic>\u03ba<\/jats:italic>B\u2010dependent luciferase expression equally. Dexamethasone treatment reduced luciferase expression stimulated by both IL\u20101<jats:italic>\u03b1<\/jats:italic> and thrombin.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The GM\u2010CSF mRNA half life was markedly prolonged by IL\u20101<jats:italic>\u03b1<\/jats:italic> compared to thrombin. This IL\u20101<jats:italic>\u03b1<\/jats:italic>\u2010induced GM\u2010CSF mRNA stability was prevented by either dexamethasone or the p38<jats:sup>MAPK<\/jats:sup> inhibitor, SB203580, neither of which influenced GM\u2010CSF mRNA stability in thrombin\u2010treated cells. Dexamethasone inhibited p38<jats:sup>MAPK<\/jats:sup> phosphorylation in IL\u20101<jats:italic>\u03b1<\/jats:italic>\u2010stimulated ASM, whereas thrombin does not stimulate p38<jats:sup>MAPK<\/jats:sup> phosphorylation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These data suggest that the mechanism underlying the greater potency and efficacy of glucocorticoids in reducing GM\u2010CSF synthesis stimulated by IL\u20101<jats:italic>\u03b1<\/jats:italic> depends on inhibition of the involvement of p38<jats:sup>MAPK<\/jats:sup>\u2010induced increases in GM\u2010CSF message stability.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2005) <jats:bold>145<\/jats:bold>, 123\u2013131. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0706174\">10.1038\/sj.bjp.0706174<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0706174","type":"journal-article","created":{"date-parts":[[2005,2,28]],"date-time":"2005-02-28T09:48:19Z","timestamp":1109584099000},"page":"123-131","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Stimulus\u2010dependent glucocorticoid\u2010resistance of GM\u2010CSF production in human cultured airway smooth muscle"],"prefix":"10.1111","volume":"145","author":[{"given":"Thai","family":"Tran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren J","family":"Fernandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Schuliga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trudi","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Landells","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alastair G","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"L372","article-title":"Glucocorticoid regulation of GM\u2010CSF: evidence for transcriptional mechanisms in airway epithelial cells","volume":"275","author":"ADKINS K.K.","year":"1998","journal-title":"Am. 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