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In this report, we show that PGE<jats:sub>2<\/jats:sub>\u2010stimulated IL\u20106 release in U373\u2003MG human astroglioma cells and primary rat astrocytes. PGE<jats:sub>2<\/jats:sub>\u2010induced intracellular cAMP formation was mediated via prostaglandin\u2003E receptor\u20032 (EP2), but inhibition of cAMP formation and protein kinase\u2003A or blockade of EP1\/EP2 receptors did not affect PGE<jats:sub>2<\/jats:sub>\u2010induced IL\u20106 synthesis. This indicates that the cAMP pathway is not part of PGE<jats:sub>2<\/jats:sub>\u2010induced signal transduction cascade leading to IL\u20106 release. The EP3\/EP1\u2010receptor agonist sulprostone failed to induce IL\u20106 release, suggesting an involvement of EP4\u2010like receptors. PGE<jats:sub>2<\/jats:sub>\u2010activated p38 mitogen\u2010activated kinase (p38 MAPK) and protein kinase\u2003C (PKC). PGE<jats:sub>2<\/jats:sub>\u2010induced IL\u20106 synthesis was inhibited by specific inhibitors of p38 MAPK (SB202190) and PKC (GF203190X). Although, up to now, EP receptors have only rarely been linked to p38 MAPK or PKC activation, these results suggest that PGE<jats:sub>2<\/jats:sub> induces IL\u20106 via an EP4\u2010like receptor by the activation of PKC and p38 MAPK via an EP4\u2010like receptor independently of cAMP.<\/jats:p>","DOI":"10.1046\/j.1471-4159.2001.00652.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T06:57:47Z","timestamp":1047452267000},"page":"950-958","source":"Crossref","is-referenced-by-count":94,"title":["Mechanisms of prostaglandin E2\u2010induced interleukin\u20106 release in astrocytes: possible involvement of EP4\u2010like receptors, p38 mitogen\u2010activated protein kinase and protein kinase C"],"prefix":"10.1111","volume":"79","author":[{"given":"Bernd L.","family":"Fiebich","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Schleicher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivia","family":"Spleiss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Czygan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"H\u00fcll","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,7,7]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(98)01349-6"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(95)00146-A"},{"key":"e_1_2_7_4_1","first-page":"F624","article-title":"PKC isoforms in rat medullary thick ascending limb: selective activation of the delta\u2010isoform by PGE2","volume":"272","author":"Aristimuno P. 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