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Regulation of microglia activity by glaucocalyxin-A: attenuation of lipopolysaccharide-stimulated neuroinflammation through NF-κB and p38 MAPK signaling pathways.

Abstract

Microglial cells are the resident macrophages and intrinsic arm of the central nervous system innate immune defense. Microglial cells become activated in response to injury, infection, environmental toxins, and other stimuli that threaten neuronal survival. Therefore, regulating microglial activation may have therapeutic benefits that lead to alleviating the progression of inflammatory-mediated neurodegeneration. In the present study, we investigated the effect of glaucocalyxin A (GLA) isolated from Rabdosia japonica on the production of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated primary microglia and BV-2 cells. GLA significantly inhibited LPS-induced production of nitric oxide and reversed the morphological changes in primary microglia. Further, GLA suppressed expression of inducible nitric oxide synthase and cyclooxygenase-2 dose-dependently at the mRNA and protein levels. The production of proinflammatory cytokines such as tumor necrosis factor-α, interleukin-1β (IL)-1β, and IL-6 were inhibited by suppressing their transcriptional activity. Furthermore, GLA suppressed nuclear factor-κB activation by blocking degradation of IκB-α and inhibited the induction of lipocalin-2 expression in LPS-stimulated BV-2 cells. Mechanistic study revealed that the inhibitory effects of GLA were accompanied by blocking the p38 mitogen activated protein kinase signaling pathway in activated microglia. In conclusion, given that microglial activation contributes to the pathogenesis of neurodegenerative diseases, GLA could be developed as a potential therapeutic agent for treating microglia-mediated neuroinflammatory diseases.

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  • Authors+Show Affiliations

    ,

    Department of Biotechnology, College of Biomedical and Health Science, Konkuk University, Chungju, South Korea.

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    Source

    PloS one 8:2 2013 pg e55792

    MeSH

    Animals
    Cells, Cultured
    Diterpenes, Kaurane
    Drugs, Chinese Herbal
    Interleukin-1beta
    Interleukin-6
    Lipopolysaccharides
    Microglia
    NF-kappa B
    Nitric Oxide
    Rats
    Rats, Sprague-Dawley
    Signal Transduction
    Tumor Necrosis Factor-alpha
    p38 Mitogen-Activated Protein Kinases

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    23393601

    Citation

    Kim, Byung-Wook, et al. "Regulation of Microglia Activity By glaucocalyxin-A: Attenuation of Lipopolysaccharide-stimulated Neuroinflammation Through NF-κB and P38 MAPK Signaling Pathways." PloS One, vol. 8, no. 2, 2013, pp. e55792.
    Kim BW, Koppula S, Hong SS, et al. Regulation of microglia activity by glaucocalyxin-A: attenuation of lipopolysaccharide-stimulated neuroinflammation through NF-κB and p38 MAPK signaling pathways. PLoS ONE. 2013;8(2):e55792.
    Kim, B. W., Koppula, S., Hong, S. S., Jeon, S. B., Kwon, J. H., Hwang, B. Y., ... Choi, D. K. (2013). Regulation of microglia activity by glaucocalyxin-A: attenuation of lipopolysaccharide-stimulated neuroinflammation through NF-κB and p38 MAPK signaling pathways. PloS One, 8(2), pp. e55792. doi:10.1371/journal.pone.0055792.
    Kim BW, et al. Regulation of Microglia Activity By glaucocalyxin-A: Attenuation of Lipopolysaccharide-stimulated Neuroinflammation Through NF-κB and P38 MAPK Signaling Pathways. PLoS ONE. 2013;8(2):e55792. PubMed PMID: 23393601.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Regulation of microglia activity by glaucocalyxin-A: attenuation of lipopolysaccharide-stimulated neuroinflammation through NF-κB and p38 MAPK signaling pathways. AU - Kim,Byung-Wook, AU - Koppula,Sushruta, AU - Hong,Seong-Su, AU - Jeon,Sae-Bom, AU - Kwon,Ji-Hye, AU - Hwang,Bang-Yeon, AU - Park,Eun-Jung, AU - Choi,Dong-Kug, Y1 - 2013/02/05/ PY - 2012/10/04/received PY - 2012/12/30/accepted PY - 2013/2/9/entrez PY - 2013/2/9/pubmed PY - 2013/8/27/medline SP - e55792 EP - e55792 JF - PloS one JO - PLoS ONE VL - 8 IS - 2 N2 - Microglial cells are the resident macrophages and intrinsic arm of the central nervous system innate immune defense. Microglial cells become activated in response to injury, infection, environmental toxins, and other stimuli that threaten neuronal survival. Therefore, regulating microglial activation may have therapeutic benefits that lead to alleviating the progression of inflammatory-mediated neurodegeneration. In the present study, we investigated the effect of glaucocalyxin A (GLA) isolated from Rabdosia japonica on the production of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated primary microglia and BV-2 cells. GLA significantly inhibited LPS-induced production of nitric oxide and reversed the morphological changes in primary microglia. Further, GLA suppressed expression of inducible nitric oxide synthase and cyclooxygenase-2 dose-dependently at the mRNA and protein levels. The production of proinflammatory cytokines such as tumor necrosis factor-α, interleukin-1β (IL)-1β, and IL-6 were inhibited by suppressing their transcriptional activity. Furthermore, GLA suppressed nuclear factor-κB activation by blocking degradation of IκB-α and inhibited the induction of lipocalin-2 expression in LPS-stimulated BV-2 cells. Mechanistic study revealed that the inhibitory effects of GLA were accompanied by blocking the p38 mitogen activated protein kinase signaling pathway in activated microglia. In conclusion, given that microglial activation contributes to the pathogenesis of neurodegenerative diseases, GLA could be developed as a potential therapeutic agent for treating microglia-mediated neuroinflammatory diseases. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/23393601/Regulation_of_microglia_activity_by_glaucocalyxin_A:_attenuation_of_lipopolysaccharide_stimulated_neuroinflammation_through_NF_κB_and_p38_MAPK_signaling_pathways_ L2 - http://dx.plos.org/10.1371/journal.pone.0055792 DB - PRIME DP - Unbound Medicine ER -