title: 3,3'-Diindolylmethane inhibits lipopolysaccharide-induced microglial hyperactivation and attenuates brain inflammation.
abstract: Recent studies have revealed that microglial hyperactivation and neuroinflammation are implicated in development and progression of neurodegenerative diseases. In this study, we examined the beneficial effects of 3,3'-diindolylmethane (DIM) and indole-3-carbinol (I3C), dietary components found in cruciferous vegetables, on brain inflammation. DIM, a major metabolite of I3C, suppressed lipopolysaccharide (LPS)-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 in BV-2 microglia, but I3C did not. DIM, but not I3C, attenuated DNA-binding activity of nuclear factor-κB (NF-κB) and phosphorylation of inhibitor of κB, suggesting that DIM might inhibit microglial hyperactivation by attenuating inflammatory transcription factor NF-κB. In addition, DIM, but not I3C, protected primary cortical neurons from inflammatory toxicity induced by the conditioned media from LPS-stimulated BV-2 microglia, indicating that DIM might attenuate microglial hyperactivation-mediated neuronal death. In an in vivo model of neuroinflammation, DIM suppressed LPS-induced brain inflammation in mouse hippocampus, as determined by the number of Iba-1-positive cells and the mRNA expression of F4/80. Taken together, these results suggest that DIM may have beneficial potential against brain inflammation and neurodegenerative diseases through the negative regulation of the NF-κB signal pathway in microglia.
authors.affiliation: * WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul 151-742, Republic of Korea;
authors.forename: Hyo Won
authors.initials: HW
authors.lastname: Kim
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kim
authors.forename: Jaekyoon
authors.initials: J
authors.lastname: Kim
authors.forename: Siyoung
authors.initials: S
authors.lastname: Lee
authors.forename: Bo-Ryoung
authors.initials: BR
authors.lastname: Choi
authors.forename: Jung-Soo
authors.initials: JS
authors.lastname: Han
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.forename: Hyong Joo
authors.initials: HJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007211:Indoles / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C491049:Aif1 protein, mouse; D000893:Anti-Inflammatory Agents; D000943:Antigens, Differentiation; D002135:Calcium-Binding Proteins; D017077:Culture Media, Conditioned; D007211:Indoles; D008070:Lipopolysaccharides; D008840:Microfilament Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; C036763:monocyte-macrophage differentiation antigen; C016517:indole-3-carbinol; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C016392:3,3'-diindolylmethane
keywords: 3; 3′-diindolylmethane; NF-κB; brain inflammation.; cruciferous vegetables; indole-3-carbinol; microglia