Effects of Bothrops asper snake venom on the expression of cyclooxygenases and production of prostaglandins by peritoneal leukocytes in vivo, and by isolated neutrophils and macrophages in vitro.
In this study, the ability of Bothrops asper snake venom (BaV) to increase the production of prostaglandins PGE(2) and PGD(2) was assessed in a mouse model in vivo and in inflammatory cells in vitro. In addition, the expressions of COX-1 and COX-2 were assessed. BaV induced an increment in the in vivo synthesis of PGE(2) and PGD(2), together with an enhanced expression of COX-2, but not of COX-1. However, enzymatic activities of COX-1 and COX-2 were increased. Incubation of isolated macrophages and neutrophils with a sub-cytotoxic concentration of BaV in vitro resulted in increased release of PGE(2) and PGD(2) by macrophages and PGE(2) by neutrophils, concomitantly with an increment in the expression of COX-2, but not of COX-1 by both cell types. Our results demonstrate the ability of BaV to promote the expression of COX-2 and to induce the synthesis of proinflammatory prostaglandins. Macrophages and neutrophils may be important targets for this venom under in vivo situation.
Moreira
Vanessa
V
Laboratorio de Farmacologia, Instituto Butantan, Av. Vital Brasil, 1500, CEP 05503-900, Sao Paulo, SP, Brazil.
Gutiérrez
José María
JM
Amaral
Rafaela Bacci
RB
Zamunér
Stella Regina
SR
Teixeira
Catarina de Fátima Pereira
Cde F
D000818:Animals; D001202:Ascitic Fluid / Q000378:metabolism; D055162:Biocatalysis; D017837:Bothrops; D002470:Cell Survival / Q000187:drug effects; D003435:Crotalid Venoms / Q000494:pharmacology*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010529:Peritoneal Cavity / Q000166:cytology; D015230:Prostaglandin D2 / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism*
D003435:Crotalid Venoms; D008565:Membrane Proteins; D011453:Prostaglandins; C077623:Ptgs2 protein, mouse; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D015232:Dinoprostone; D015230:Prostaglandin D2