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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Moreira, Vanessa [1] ; Lomonte, Bruno [2] ; Ramirez Vinolo, Marco Aurelio [3] ; Curi, Rui [4] ; Maria Gutierrez, Jose [2] ; Teixeira, Catarina [1]
Total Authors: 6
[1] Inst Butantan, Farmacol Lab, BR-05503900 Sao Paulo - Brazil
[2] Univ Costa Rica, Fac Microbiol, Inst Clodomiro Picado, San Jose - Costa Rica
[3] Univ Estadual Campinas, Inst Biol, Dept Genet Evolucao & Bioagentes, Campinas, SP - Brazil
[4] Univ Sao Paulo, Inst Ciencias Biomed, Dept Fisiol, BR-05508 Sao Paulo - Brazil
Total Affiliations: 4
Document type: Journal article
Source: Mediators of Inflammation; 2014.
Web of Science Citations: 9

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: 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 type: Research Grants - Young Investigators Grants
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 type: Scholarships in Brazil - Post-Doctorate