Benzyl isothiocyanate inhibits inflammasome activation in E-coli LPS-stimulated BV2 cells

초록

Inflammasomes are multi-protein complexes that play a crucial role in innate immune responses. Benzyl isothiocyanate (BITC) is a naturally occurring compound found in cruciferous vegetables, and BITC exhibits potential as a chemopreventive agent. However, whether BITC exerts inflammasome-mediated regulatory effects on neuroinflammation is unknown. In this study, we examined the effects of BITC on inflammasome-mediated interleukin-1 (IL-1) production in E. coli lipopolysaccharide (LPS)-stimulated BV2 microglial cells. IL-1 production is tightly regulated at the post-translational level through the inflammasoume. We measured the levels of IL-1 produced from the LPS-exposed BV2 microglial cells using enzyme-linked immunosorbent assays (ELISAs). The BITC regulatory mechanisms in inflammasome-mediated cellular signaling pathways were examined by RT-PCR, western blot analysis and electrophoretic mobility shift assays. BITC inhibited the secretion of IL-1 induced by LPS in the BV2 microglial cells. BITC inhibited inflammasome activation and NLR family, pyrin domain containing 3 (NLRP3)-mediated caspase-1 activation, and decreased the levels of inflammasome activation pro-inflammatory mediators, including mitochondrial reactive oxygen species (ROS) and adenosine triphosphate (ATP) secretion in the LPS-stimulated BV2 microglial cells. Furthermore, we demonstrated that nuclear factor-B (NF-B) activation induced by LPS was inhibited by BITC, which may contribute to the attenuated secretion of IL-1. These BITC-mediated inhibitory effects on IL-1 expression may thus regulate neuroinflammation through the inflammasome-mediated signaling pathway.

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