An Asp49 phospholipase A(2) from snake venom induces cyclooxygenase-2 expression and prostaglandin E-2 production via activation of NF-kappa B, p38MAPK, and PKC in macrophages
M. A. R. Vinolo, R. Curi, B. Lomonte, V. Moreira, J. M. Gutierrez, C. Teixeira
ARTIGO
Inglês
Agradecimentos: Vicerrectoria de Investigacion (Universidad de Costa Rica)
Phospholipases A(2) (PLA(2)) are key enzymes for production of lipid mediators. We previously demonstrated that a snake venom sPLA(2) named MT-III leads to prostaglandin (PG)E-2 biosynthesis in macrophages by inducing the expression of cyclooxygenase-2 (COX-2). Herein, we explored the molecular...
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Phospholipases A(2) (PLA(2)) are key enzymes for production of lipid mediators. We previously demonstrated that a snake venom sPLA(2) named MT-III leads to prostaglandin (PG)E-2 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-kappa B in isolated macrophages. By using NF-kappa B selective inhibitors, the involvement of this factor in MT-III-induced COX-2 expression and PGE(2) production was demonstrated. Moreover, MT-III-induced COX-2 protein expression and PGE(2) 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-kappa B induced by MT-III. Altogether, these results show for the first time that the induction of COX-2 protein expression and PGE(2) release, which occur via NF-kappa B activation induced by the sPLA(2)-MT-III in macrophages, are modulated by p38MAPK and PKC, but not by PI3K signaling proteins
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FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP
02/13863-2; 07/03336-9; 07/03337-5; 12/10653-9
CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ
306099/2008-0
Aberto
DOI: https://doi.org/10.1155/2014/105879
Texto completo: https://www.hindawi.com/journals/mi/2014/105879/
An Asp49 phospholipase A(2) from snake venom induces cyclooxygenase-2 expression and prostaglandin E-2 production via activation of NF-kappa B, p38MAPK, and PKC in macrophages
M. A. R. Vinolo, R. Curi, B. Lomonte, V. Moreira, J. M. Gutierrez, C. Teixeira
An Asp49 phospholipase A(2) from snake venom induces cyclooxygenase-2 expression and prostaglandin E-2 production via activation of NF-kappa B, p38MAPK, and PKC in macrophages
M. A. R. Vinolo, R. Curi, B. Lomonte, V. Moreira, J. M. Gutierrez, C. Teixeira
Fontes
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Mediators of inflammation (2014), n. art. 105879 |