title: Benzyl isothiocyanate inhibits inflammasome activation in E. coli LPS-stimulated BV2 cells.
abstract: 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-1β (IL-1β) production in E. coli lipopolysaccharide (LPS)-stimulated BV2 microglial cells. IL-1β production is tightly regulated at the post-translational level through the inflammasoume. We measured the levels of IL-1β 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-1β 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-κB (NF-κB) activation induced by LPS was inhibited by BITC, which may contribute to the attenuated secretion of IL-1β. These BITC-mediated inhibitory effects on IL-1β expression may thus regulate neuroinflammation through the inflammasome-mediated signaling pathway.
authors.affiliation: Department of Molecular Microbiology and Immunology, Warren Alpert School of Medicine, Providence, RI 02912, USA.
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Lee
authors.affiliation: National Marine Biodiversity Institute of Korea, Seocheon, Republic of Korea.
authors.forename: Dae-Sung
authors.initials: DS
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, and Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan, Republic of Korea.
authors.forename: Won-Kyo
authors.initials: WK
authors.lastname: Jung
authors.affiliation: National Marine Biodiversity Institute of Korea, Seocheon, Republic of Korea.
authors.forename: Jong Su
authors.initials: JS
authors.lastname: Yoo
authors.affiliation: National Marine Biodiversity Institute of Korea, Seocheon, Republic of Korea.
authors.forename: Mi-Jin
authors.initials: MJ
authors.lastname: Yim
authors.affiliation: Department of Biochemistry, College of Oriental Medicine, Dongeui University, Busan, Republic of Korea.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, Inje University, Busan, Republic of Korea.
authors.forename: Saegwang
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, Inje University, Busan, Republic of Korea.
authors.forename: Su-Kil
authors.initials: SK
authors.lastname: Seo
authors.affiliation: Department of Internal Medicine, Busan Paik Hospital, College of Medicine, Inje University, Busan, Republic of Korea.
authors.forename: Jung Sik
authors.initials: JS
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Busan Paik Hospital, College of Medicine, Inje University, Busan, Republic of Korea.
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Lee
authors.affiliation: Department of Physiology, Kangwon National University School of Medicine, Chuncheon, Republic of Korea.
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, Inje University, Busan, Republic of Korea.
authors.forename: Il-Whan
authors.initials: IW
authors.lastname: Choi
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D020170:Caspase 1 / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation; D004926:Escherichia coli / Q000737:chemistry*; D015870:Gene Expression / Q000187:drug effects; D058847:Inflammasomes / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D017879:Isothiocyanates / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D058847:Inflammasomes; D053583:Interleukin-1beta; D017879:Isothiocyanates; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D017382:Reactive Oxygen Species; C031403:benzyl isothiocyanate; D000255:Adenosine Triphosphate; D020170:Caspase 1