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We previously demonstrated that a snake venom sPLA<jats:sub>2<\/jats:sub>named MT-III leads to prostaglandin (PG)E<jats:sub>2<\/jats:sub>biosynthesis in macrophages by inducing the expression of cyclooxygenase-2 (COX-2). Herein, we explored the molecular mechanisms and signaling pathways leading to these MT-III-induced effects. Results demonstrated that MT-III induced activation of the transcription factor NF-<jats:italic>\u03ba<\/jats:italic>B in isolated macrophages. By using NF-<jats:italic>\u03ba<\/jats:italic>B selective inhibitors, the involvement of this factor in MT-III-induced COX-2 expression and PGE<jats:sub>2<\/jats:sub>production was demonstrated. Moreover, MT-III-induced COX-2 protein expression and PGE<jats:sub>2<\/jats:sub>release were attenuated by pretreatment of macrophages with SB202190, and Ly294002, and H-7-dihydro compounds, indicating the involvement of p38MAPK, PI3K, and PKC pathways, respectively. Consistent with this, MT-III triggered early phosphorylation of p38MAPK, PI3K, and PKC. Furthermore, SB202190, H-7-dihydro, but not Ly294002 treatment, abrogated activation of NF-<jats:italic>\u03ba<\/jats:italic>B induced by MT-III. Altogether, these results show for the first time that the induction of COX-2 protein expression and PGE<jats:sub>2<\/jats:sub>release, which occur via NF-<jats:italic>\u03ba<\/jats:italic>B activation induced by the sPLA<jats:sub>2<\/jats:sub>-MT-III in macrophages, are modulated by p38MAPK and PKC, but not by PI3K signaling proteins.<\/jats:p>","DOI":"10.1155\/2014\/105879","type":"journal-article","created":{"date-parts":[[2014,4,6]],"date-time":"2014-04-06T21:01:25Z","timestamp":1396818085000},"page":"1-10","source":"Crossref","is-referenced-by-count":27,"title":["An Asp49 Phospholipase A<sub>2<\/sub>from Snake Venom Induces Cyclooxygenase-2 Expression and Prostaglandin E<sub>2<\/sub>Production via Activation of NF-<i>\u03ba<\/i>B, p38MAPK, and PKC in Macrophages"],"prefix":"10.1155","volume":"2014","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4048-1967","authenticated-orcid":true,"given":"Vanessa","family":"Moreira","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio 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