Moreira Vanessa, Gutiérrez José María, Amaral Rafaela Bacci, Zamunér Stella Regina, Teixeira Catarina de Fátima Pereira
Laboratorio de Farmacologia, Instituto Butantan, Av. Vital Brasil, 1500, CEP 05503-900, Sao Paulo, SP, Brazil.
Prostaglandins Leukot Essent Fatty Acids. 2009 Feb-Mar;80(2-3):107-14. doi: 10.1016/j.plefa.2008.11.009. Epub 2009 Jan 19.
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.
在本研究中,在体内小鼠模型和体外炎症细胞中评估了矛头蝮蛇毒(BaV)增加前列腺素PGE(2)和PGD(2)产生的能力。此外,还评估了COX-1和COX-2的表达。BaV诱导体内PGE(2)和PGD(2)合成增加,同时COX-2表达增强,但COX-1未增强。然而,COX-1和COX-2的酶活性增加。体外将分离的巨噬细胞和中性粒细胞与亚细胞毒性浓度的BaV孵育,导致巨噬细胞释放PGE(2)和PGD(2)增加,中性粒细胞释放PGE(2)增加,同时两种细胞类型中COX-2的表达增加,但COX-1未增加。我们的结果证明了BaV促进COX-2表达和诱导促炎前列腺素合成的能力。在体内情况下,巨噬细胞和中性粒细胞可能是这种蛇毒的重要靶标。