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Prostaglandin E<jats:sub>2<\/jats:sub> (PGE<jats:sub>2<\/jats:sub>), an eicosanoid also associated with inflammation and cancer, has recently been shown to induce OSM expression. We report here that OSM in turn induces PGE<jats:sub>2<\/jats:sub> production by astrocytes and astroglioma cells. More importantly, in combination with the inflammatory mediators IL\u20101\u03b2, tumor necrosis factor\u2010\u03b1, and lipopolysaccharide, OSM exhibits a striking synergy, resulting in up to 50\u2010fold higher PGE<jats:sub>2<\/jats:sub> production by astrocytes, astroglioma, and neuroblastoma cell lines. Enhanced PGE<jats:sub>2<\/jats:sub> production by OSM and IL\u20101\u03b2 treatment is explained by their effect on cyclooxygenase\u20102 (COX\u20102), an enzyme that catalyzes the committed step in PGE<jats:sub>2<\/jats:sub> synthesis. Of the enzymes involved in PGE<jats:sub>2<\/jats:sub> biosynthesis, only COX\u20102 mRNA and protein levels are synergistically amplified by OSM and IL\u20101\u03b2. Nuclear run\u2010on assays demonstrate that OSM and IL\u20101\u03b2 synergistically upregulate transcription of the COX\u20102 gene, and the mRNA stability assay indicates that COX\u20102 mRNA is posttranscriptionally stabilized by OSM and IL\u20101\u03b2. To effect synergy on the PGE<jats:sub>2<\/jats:sub> level, OSM signals in part through its gp130\/OSMR\u03b2 receptor, since neutralizing antibodies against gp130 and OSMR\u03b2, but not LIFR\u03b2, decrease PGE<jats:sub>2<\/jats:sub> production in response to OSM plus IL\u20101\u03b2. SB202190 and U0126, inhibitors of p38 MAPK and ERK1\/2 activation, respectively, inhibit IL\u20101\u03b2 and OSM upregulation of COX\u20102 and PGE<jats:sub>2<\/jats:sub>, indicating that these MAPK cascades are utilized by both stimuli. This mechanism of PGE<jats:sub>2<\/jats:sub> amplification may be active in brain pathologies where both OSM and IL\u20101\u03b2 are present, such as glioblastomas and multiple sclerosis. GLIA 42:433\u2013446, 2003. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.10182","type":"journal-article","created":{"date-parts":[[2003,4,30]],"date-time":"2003-04-30T10:01:40Z","timestamp":1051696900000},"page":"433-446","source":"Crossref","is-referenced-by-count":49,"title":["Oncostatin M enhances the expression of prostaglandin E<sub>2<\/sub> and cyclooxygenase\u20102 in astrocytes: Synergy with interleukin\u20101\u03b2, tumor necrosis factor\u2010\u03b1, and bacterial lipopolysaccharide"],"prefix":"10.1002","volume":"42","author":[{"given":"Pavle","family":"Repovic","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaihong","family":"Mi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etty 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