Journal
TOXICOLOGICAL SCIENCES
Volume 137, Issue 1, Pages 158-167Publisher
OXFORD UNIV PRESS
DOI: 10.1093/toxsci/kft240
Keywords
3; 3-diindolylmethane; indole-3-carbinol; cruciferous vegetables; NF-B; microglia; brain inflammation
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Funding
- National Research Foundation of Korea (NRF) [2012R1A1A3011954]
- Ministry of Education, Science and Technology
- Ministry of Knowledge Economy, Republic of Korea [10033818]
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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-B (NF-B) and phosphorylation of inhibitor of B, suggesting that DIM might inhibit microglial hyperactivation by attenuating inflammatory transcription factor NF-B. 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 hyperactivationmediated 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-B signal pathway in microglia.
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