LTB4 and PGE2 modulate the release of MIP-1α and IL-1β by cells stimulated withBothropssnake venoms


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Abstract

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 B4 (LTB4) and prostaglandin E2 (PGE2) regulate macrophage production of interleukin-1β (IL-1β) 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-1α) and IL-1β 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-κB activation in THP-1 cells. Furthermore, we observed that treatment of THP-1 and AMJ2-C11 cell lines with exogenous PGE2 reduces MIP-1α production, while increasing IL-1β production in cells stimulated by B. jararaca or B. jararacussu venoms. Interestingly, exogenous LTB4 had the opposite effect by reducing IL-1β and increasing MIP-1α 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.Graphical abstractHighlightsPGE2 and LTB4 modulate MIP-1α and IL-1β production by innate immune cells in response to Bothrops venoms.Bothrops venoms induce NF-κB activation in human monocytes.PGE2 potentiates and LTB4 restrains NF-κB activation in human monocytes stimulated with Bothrops venoms.

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