Mecanismos envolvidos na produção e liberação de TNF-α induzidas pela BaP1

Abstract

Metalloproteinases are abundant enzymes in snake venoms of Viperidae family and are relevant in the pathophysiology of envenomation, by their hemorrhagic, fibrinogenolytic and inflammatory activities. From Bothrops asper snake venom was isolated the metalloproteinase BaP1, with molecular weight of 22.7 KDa, weak hemorrhagic action and containing only the catalytic domain of metalloproteinases. Previous studies of our group have shown that BaP1 induces important inflammatory events in vivo and in vitro, inducing the release of inflammatory mediators, such as TNF-α (tumor necrosis factor alpha) by macrophages, important cells of the immune system. ADAM-17 or TACE (TNF-α converting enzyme) is responsible for the release of active TNF-α from its precursor. However, the mechanisms involved in the processing of TNF-α, under the action of BaP1, are unknown. In the present study was demonstrated that macrophages of the RAW 264-7 lineage, pretreated or not with SN50 compound, the nuclear transcription factor NF-κB inhibitor, and stimulated with BaP1 (12.5 μg / mL) for a period of 6 hours, showed a significant decrease in protein expression and the release of TNF-α, when compared to the negative control (culture medium RPMI). Pretreatment of RAW 264-7 cells with the TACE inhibitor, TAPI-1 (200 nM), and incubation with BaP1 (12.5 μg / mL) or RPMI, for 3 h, significantly decreased TNF-α release, when compared to the control group (RPMI). The present study demonstrated that the activation of NF-κB is an important mechanism involved in the processing of TNF-α, induced by BaP1 in RAW 264-7 cells and the release of TNF-α induced by BaP1 is dependent on the action of ADAM-17.