Journal of Ginseng Research

  • 제46권5호
  • /
  • Pages.675-682
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  • 2022
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  • 1226-8453(pISSN)
  • /
  • 2093-4947(eISSN)
고려인삼학회 (The Korean Society of Ginseng)
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A novel mechanism of Korean Red Ginseng-mediated anti-inflammatory action via targeting caspase-11 non-canonical inflammasome in macrophages

  • Min, Ji-Hyun (Department of Life Sciences, Kyonggi University) ;
  • Cho, Hui-Jin (Department of Life Sciences, Kyonggi University) ;
  • Yi, Young-Su (Department of Life Sciences, Kyonggi University)
  • 투고 : 2021.11.10
  • 심사 : 2021.12.26
  • 발행 : 2022.09.01
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초록

Background: Korean Red Ginseng (KRG) was reported to play an anti-inflammatory role, however, previous studies largely focused on the effects of KRG on priming step, the inflammation-preparing step, and the anti-inflammatory effect of KRG on triggering, the inflammation-activating step has been poorly understood. This study demonstrated anti-inflammatory role of KRG in caspase-11 non-canonical inflammasome activation in macrophages during triggering of inflammatory responses. Methods: Caspase-11 non-canonical inflammasome-activated J774A.1 macrophages were established by priming with Pam3CSK4 and triggering with lipopolysaccharide (LPS). Cell viability and pyroptosis were examined by MTT and lactate dehydrogenase (LDH) assays. Nitric oxide (NO)-inhibitory effect of KRG was assessed using a NO production assay. Expression and proteolytic cleavage of proteins were examined by Western blotting analysis. In vivo anti-inflammatory action of KRG was evaluated with the LPS-injected sepsis model in mice. Results: KRG reduced LPS-stimulated NO production in J774A.1 cells and suppressed pyroptosis and IL-1β secretion in caspase-11 non-canonical inflammasome-activated J774A.1 cells. Mechanistic studies demonstrated that KRG suppressed the direct interaction between LPS and caspase-11 and inhibited proteolytic processing of both caspase-11 and gasdermin D in caspase-11 non-canonical inflammasome-activated J774A.1 cells. Furthermore, KRG significantly ameliorated LPS-mediated lethal septic shock in mice. Conclusion: The results demonstrate a novel mechanism of KRG-mediated anti-inflammatory action that operates through targeting the caspase-11 non-canonical inflammasome at triggering step of macrophage-mediated inflammatory response.

키워드

과제정보

This work was supported by Kyonggi University's Graduate Research Assistantship 2021 and a grant from the Korean Society of Ginseng (2020).

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