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Since G\u2010CSF release is mediated, at least in part, by TNF\u2010\u03b1 formation, we investigated whether drugs suppressing TNF\u2010\u03b1 also impair G\u2010CSF production. Surprisingly, G\u2010CSF formation was enhanced in lipopolysaccharide (LPS)\u2010stimulated blood from a pentoxifylline\u2010treated patient. In the presence of dibutyryl\u2010cAMP, forskolin, tolafentrine or 3\u2010isobutyl\u20101\u2010methylxanthine, LPS\u2010induced G\u2010CSF formation was enhanced in THP\u20101 cells, primary monocytes and whole blood. Correspondingly,rp\u20108\u2010bromo\u2010cAMP suppressed LPS\u2010induced G\u2010CSF release. Addition of prostaglandin\u2004E<jats:sub>2<\/jats:sub> enhanced and indomethacin suppressed G\u2010CSF formation. Reporter gene studies showed that dibutyryl\u2010cAMP enhanced LPS\u2010induced G\u2010CSF promoter activity, indicating a transcriptional up\u2010regulation. Furthermore, disruption of a newly identified putative cAMP\u2010responsive element (CRE) in the G\u2010CSF promoter demonstrated the regulatory role for G\u2010CSF gene transcription. In conclusion, endogenous G\u2010CSF formation critically depends on both TNF\u2010\u03b1 and cyclooxygenase products, exerting effects via cAMP and the CREin the G\u2010CSF promoter. This might have bearing for drug side effects, putative G\u2010CSF mimetics and our understanding of G\u2010CSF immunobiology.<\/jats:p>","DOI":"10.1002\/eji.200323923","type":"journal-article","created":{"date-parts":[[2003,7,22]],"date-time":"2003-07-22T17:11:39Z","timestamp":1058893899000},"page":"2287-2296","source":"Crossref","is-referenced-by-count":15,"title":["Cyclic AMP increases endogenous granulocyte colony\u2010stimulating factor formation in monocytes and THP\u20101 macrophages despite attenuated TNF\u2010\u03b1 formation"],"prefix":"10.1002","volume":"33","author":[{"given":"Lars","family":"Hareng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Meergans","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonja","family":"von Aulock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans\u2010Dieter","family":"Volk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Hartung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,7,21]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/BFb0032323"},{"key":"e_1_2_7_2_2","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1177\/096805199500200308","article-title":"G\u2010CSF \u2013 an anti\u2010inflammatory cytokine.","volume":"2","author":"Hartung T.","year":"1995","journal-title":"J. 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