LTB4 and PGE(2) modulate the release of MIP-1 alpha and IL-1 beta by cells stimulated with Bothrops snake venoms

Envenomation by Bothrops snakes promotes the release of inflammatory mediators, whose effects during this context are not well understood. These mediators include chemokines, cytokines and eicosanoids. Indeed, Bothrops snake envenomation results in local and systemic perturbations, including leukocyte recruitment, edema, pain and extensive tissue damage. Recently, our group demonstrated that leukotriene B-4 (LTB4) and prostaglandin E-2 (PGE(2)) regulate macrophage production of interleukin-1 beta (IL-1 beta) induced by scorpion venom. Whether these molecular mechanisms also affect host cell responses to snake venoms, such as those from B. jararaca or B. jararacussu, is unknown. In this study, we demonstrate that B. jararaca or B. jararacussu venoms induce macrophage inflammatory protein 1-alpha (MIP-1 alpha) and IL-1 beta production by THP-1 (cell line of human peripheral blood monocytes) and AMJ2-C11 (cell line of mouse alveolar macrophage). We also show that venoms from both Bothrops species induce NF-kappa B activation in THP-1 cells. Furthermore, we observed that treatment of THP-1 and AMJ2-C11 cell lines with exogenous PGE(2) reduces MIP-1 alpha production, while increasing IL-1 beta production in cells stimulated by B. jararaca or B. jararacussu venoms. Interestingly, exogenous LTB4 had the opposite effect by reducing IL-1 beta and increasing MIP-1 alpha release. Our results suggest that, differential eicosanoid metabolism in myeloid cells is tightly associated with the production of cytokines and chemokines after stimulation with B. jararaca or B. jararacussu venoms. (AU)