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<p>TGR5 is a transmembrane protein that transmits the signals into intracellular space. In animals, taurocholic acid (TCA) is a natural bioactive substance in bile acid moiety regulating the TGR5-mediated anti-inflammatory immune response, which is a promising pharmacological target for treating some diseases associated with inflammation. Previously, we established that TCA-mediated immunoregulation could be implemented via modulation of expression of genes and proteins TNFα and IL-1β. In this study, we examined TGR5-mediated anti-inflammatory immune regulation by TCA. The anti-inflammatory signal transduction pathways triggered by TGR5 and the effects of TCA on TNFα and IL-1β were studied using ELISA, real-time quantitative PCR, immunofluorescence, and Western blotting. TCA specifically induced TGR5 internalization and upregulated production of cyclic AMP in a dose-dependent manner in HEK-293T cells transfected with TGR5. The effect of taurine-conjugated lithocholic acid (TLCA) on production of cyclic AMP was stronger than that of TCA in HEK-293T cells transfected with TGR5. LPS elevated expression of TNFα and IL-1β, but this proinflammatory effect was inhibited by TCA. A novel type of NR8383 cell line expressing human TGR5 (NR8383-TGR5 cells) was developed and tested. In NR8383 and NR8383-TGR5 cells, TGR5 increased expression of TNFα and IL-1β, but TCA inhibited expression of these cytokines and their mRNAs. Thus, the anti-inflammatory immune regulatory action of TCA is mediated via TGR5, which modulates expression of TNFα and IL-1β.</p>

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Anti-Inflammatory Immunoregulatory Effects of Taurocholic Acid Are Mediated by TGR5

  • 期刊论文

  • 发表日期：

    2026年1月1日

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  • Hong Su,
  • Ziying Zhang,
  • Chenguang Du,
  • Hong Guan,
  • Peifeng Li,
  • Guifang Cao,
  • Caiyun Wang

摘要

TGR5 is a transmembrane protein that transmits the signals into intracellular space. In animals, taurocholic acid (TCA) is a natural bioactive substance in bile acid moiety regulating the TGR5-mediated anti-inflammatory immune response, which is a promising pharmacological target for treating some diseases associated with inflammation. Previously, we established that TCA-mediated immunoregulation could be implemented via modulation of expression of genes and proteins TNFα and IL-1β. In this study, we examined TGR5-mediated anti-inflammatory immune regulation by TCA. The anti-inflammatory signal transduction pathways triggered by TGR5 and the effects of TCA on TNFα and IL-1β were studied using ELISA, real-time quantitative PCR, immunofluorescence, and Western blotting. TCA specifically induced TGR5 internalization and upregulated production of cyclic AMP in a dose-dependent manner in HEK-293T cells transfected with TGR5. The effect of taurine-conjugated lithocholic acid (TLCA) on production of cyclic AMP was stronger than that of TCA in HEK-293T cells transfected with TGR5. LPS elevated expression of TNFα and IL-1β, but this proinflammatory effect was inhibited by TCA. A novel type of NR8383 cell line expressing human TGR5 (NR8383-TGR5 cells) was developed and tested. In NR8383 and NR8383-TGR5 cells, TGR5 increased expression of TNFα and IL-1β, but TCA inhibited expression of these cytokines and their mRNAs. Thus, the anti-inflammatory immune regulatory action of TCA is mediated via TGR5, which modulates expression of TNFα and IL-1β.