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

Author(s)

Moreira, Vanessa ; Lomonte, Bruno ; Ramirez Vinolo, Marco Aurelio ; Curi, Rui ; Maria Gutierrez, Jose ; Teixeira, Catarina

• Document type: Journal article
• Source: Mediators of Inflammation; v. 2014, p. 10-pg., 2014-01-01.

Abstract

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. (AU)

• FAPESP's process: 07/03337-5 - Effects of two phospholipases A2, isolated from snake venom on NF-kappaB activation pathways related to COX-2 and mPGE synthase-1 expression: involvement of macrophage mannose receptors
• Grantee: Vanessa Moreira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/10653-9 - Role of short chain fatty acids and their receptor (GPR43) in the immune response to anaerobic bacteria in vivo and in vitro
• Grantee: Marco Aurélio Ramirez Vinolo
• Support Opportunities: Research Grants - Young Investigators Grants