{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T23:47:40Z","timestamp":1768434460684,"version":"3.49.0"},"reference-count":45,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,4,1]]},"abstract":"<jats:p>In the present study, IL (interleukin)-1\u03b2 increased GM-CSF (granulocyte\/macrophage colony-stimulating factor) expression from pulmonary A549 cells and primary HBE (human bronchial epithelial) cells. These responses were repressed by the glucocorticoid dexamethasone, allowing the use of A549 cells as a relevant model. IL-1\u03b2 induced GM-CSF release into the culture medium by 6\u00a0h and in cell lysates (cytosolic) at 2\u00a0h. These effects were profoundly inhibited by dexamethasone, yet IL-1\u03b2-induced GM-CSF mRNA and unspliced nRNA (nuclear RNA; a surrogate of transcription rate) were modestly inhibited by dexamethasone at times up to 2\u00a0h. Although this indicates an effect on protein synthesis, actinomycin D chase experiments also indicated post-transcriptional repression by dexamethasone. Dexamethasone-dependent mRNA repression increased with time and was prevented by translational blockade. In addition, dexamethasone and the dissociated steroid RU24858 repressed GM-CSF release in an actinomycin D-sensitive manner, thereby implicating glucocorticoid-induced gene expression. At 2\u00a0h, IL-1\u03b2-induced expression of GM-CSF protein, but not mRNA, was sensitive to the MEK [MAPK (mitogen-activated protein kinase)\/ERK (extracellular-signal-regulated kinase) kinase] inhibitors PD098059 and U0126. Although this indicates a role for the MEK\/ERK pathway in GM-CSF translation, PD098059 subsequently destabilized GM-CSF mRNA. Dexamethasone and RU24858 both reduced IL-1\u03b2-induced ERK phosphorylation and increased MKP-1 (MAPK phosphatase-1) expression. Inhibition of ERK phosphorylation was reproduced by MKP-1 overexpression and prevented by MKP-1-targeting siRNA (small interfering RNA). Since MKP-1 prevented GM-CSF expression by transcriptional, post-transcriptional and translational processes, we propose that glucocorticoids induce MKP-1 expression to reduce both MEK\/ERK activation and GM-CSF protein synthesis. Thus de novo gene expression, particularly of MKP-1, is involved in the repressive effects of glucocorticoids.<\/jats:p>","DOI":"10.1042\/bj20091038","type":"journal-article","created":{"date-parts":[[2010,1,26]],"date-time":"2010-01-26T14:04:20Z","timestamp":1264514660000},"page":"113-124","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Glucocorticoids inhibit IL-1\u03b2-induced GM-CSF expression at multiple levels: roles for the ERK pathway and repression by MKP-1"],"prefix":"10.1042","volume":"427","author":[{"given":"Robert","family":"Newton","sequence":"first","affiliation":[{"name":"Airways Inflammation Research Group, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada T2N 4N1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth\u00a0M.","family":"King","sequence":"additional","affiliation":[{"name":"Airways Inflammation Research Group, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada T2N 4N1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Xinhua Hospital, Jiaotong University, School of Medicine, Shanghai, People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher\u00a0F.","family":"Rider","sequence":"additional","affiliation":[{"name":"Airways Inflammation Research Group, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada T2N 4N1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl\u00a0J.","family":"Staples","sequence":"additional","affiliation":[{"name":"Division of Infection, Inflammation and Immunity, University of Southampton, Southampton, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil\u00a0S.","family":"Holden","sequence":"additional","affiliation":[{"name":"Airways Inflammation Research Group, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada T2N 4N1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin\u00a0W.","family":"Bergmann","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Franz Volhard Clinic, Charit\u00e9 Campus Buch, Berlin, Germany"},{"name":"Max Delbr\u00fcck Center for Molecular Medicine, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2010,3,15]]},"reference":[{"key":"2021112214323919600_B1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.ejphar.2005.12.052","article-title":"Corticosteroids: the drugs to beat","volume":"533","author":"Barnes","year":"2006","journal-title":"Eur. 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