Lithocholic acid inhibits dendritic cell activation by reducing intracellular glutathione via TGR5 signaling

Hu, Jianping; Zhang, Yiting; Yi, Shenglan; Wang, Chaokui; Huang, Xinyue; S, Pan; Yang, Jinglu; Yuan, Guangjie; Tan, Sisi; Li, Hong

doi:10.7150/ijbs.71287

Cited by 18 publications

(19 citation statements)

References 55 publications

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“…During the development and progression of PCa, NF-κB/p65 is constitutively activated, and the mechanism involves an increased phosphorylation of inhibitor of NF-κB (IκB) protein (27,28). In this study, we found GPBAR1 inhibited the phosphorylation of IkBα, which promoted p65 phosphorylation release in vivo and in vitro (29). We previously showed that PA induced PCa cell apoptosis by inhibiting NF-κB activity (18).…”

mentioning

confidence: 59%

Patchouli alcohol inhibits GPBAR1-mediated cell proliferation, apoptosis, migration, and invasion in prostate cancer

Cai¹,

Zhao²,

Ping³

et al. 2022

Transl Androl Urol

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Background: G protein-coupled bile acid receptor 1 (GPBAR1) is a G protein-coupled receptor for bile acids, which is widely expressed in many human tissues. Patchouli alcohol (PA) has been shown to have an anti-cancer effect, including in prostate cancer (PCa). This study sought to confirm the regulatory mechanism of GPBAR1 in the anti-cancer activity of PA in PCa. Methods:The SwissTargetPrediction website (Pro >0) was used to predict the target of PA. The UALCAN and The Cancer Genome Atlas-Prostate cohort was used to examine the differentially expressed genes and PCa recurrence. A gene set enrichment analysis (GSEA) was conducted to analyze the relationship between the expression of GPBAR1 and PCa proliferation, migration, and invasion. Cell proliferation, migration, and invasion were assessed by colony formation, 5-Ethynyl-2'-deoxyuridine staining, cell scratch assays, and Transwell invasion assays, respectively. A xenograft animal model was established to assess the effect of PA on tumor growth in vivo. GPBAR1 protein and apoptosis related protein expression was measured by western blot.Results: GPBAR1 was a PA target predicted by the SwissTargetPrediction website. PA inhibited the expression of GPBAR1 in PCa cells in a time-and dose-dependent manner. The abnormal expression of GPBAR1 was related to cell proliferation, migration, and invasion. Additionally, GPBAR1 overexpression promoted the cell proliferation, migration, and invasion, and inhibited the apoptosis of PCa cells. GPBAR1 silencing inhibited the cell proliferation, migration, and invasion, and promoted the apoptosis of PCa cells.High expressions of GPBAR1 suppressed tumor growth in tumor-bearing mice. Further, GPBAR1 promoted the activation of nuclear factor kappa B (NF-κB) signaling, and PA regulated the malignant phenotypes of PCa cells via the NF-κB signaling pathway mediated by GPBAR1.Conclusions: GPBAR1 is a promising drug target of PA, and was shown to regulate the proliferation, apoptosis, migration, and invasion of PCa cells through GPBAR1/NF-κB inhibition.

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mentioning

confidence: 59%

Patchouli alcohol inhibits GPBAR1-mediated cell proliferation, apoptosis, migration, and invasion in prostate cancer

Cai¹,

Zhao²,

Ping³

et al. 2022

Transl Androl Urol

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“…28 Moreover, TGR5 agonists, that is, LCA and INT-777 treatment, increased the TGR5 expression in monocyte-derived DCs of patients with Behcet's disease. 29…”

Section: In Immune Cellsmentioning

confidence: 99%

“…63 Also, TGR5 activation inhibited glutathione production and induced oxidative stress, which led to apoptosis and autophagy in DCs. 29 As a result, TGR5 activation increases the production of FoxP3 + regulatory T cells and reduces the production of effector T cells. 54 For instance, TGR5 activation of tumourassociated macrophages mediated CD8 + T-cell suppression, while TGR5 activation of macrophages co-cultured with CD4 + T cells inhibited Th1 and Th17 polarization, as well as the release of IFN-γ and IL-17 in the culture supernatant.…”

Section: Tgr5 Activation Inhibits the Adaptive Immune Responsementioning

confidence: 99%

The role of bile acid receptor TGR5 in regulating inflammatory signalling

Ye,

He,

2024

Scand J Immunol

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Takeda G protein‐coupled receptor 5 (TGR5) is a bile acid receptor, and its role in regulating metabolism after binding with bile acids has been established. Since the immune response depends on metabolism to provide biomolecules and energy to cope with challenging conditions, emerging evidence reveals the regulatory effects of TGR5 on the immune response. An in‐depth understanding of the effect of TGR5 on immune regulation can help us disentangle the interaction of metabolism and immune response, accelerating the development of TGR5 as a therapeutic target. Herein, we reviewed more than 200 articles published in the last 20 years in PubMed, to discuss the roles of TGR5 in regulating inflammatory response, the molecular mechanism, as well as existing problems. Particularly, its anti‐inflammation effect is emphasized.

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“…TGR5 and FXR are expressed in a variety of immune cells as two major receptors for BA. TGR5 has anti-inflammatory effects and reduces the production of inflammatory cytokines in monocytes, macrophages, and dendritic cells ( Hu et al, 2022 ). Activated TGR5 inhibits NLRP3 inflammasome activation via the TGR5-cAMP-PKA axis, thereby attenuating high-fat diet-induced elevated glucose tolerance, IR, and inflammatory responses ( Hu et al, 2021 ).…”

Section: Bile Acids and Type 2 Diabetes Mellitusmentioning

confidence: 99%

Bile acids-gut microbiota crosstalk contributes to the improvement of type 2 diabetes mellitus

Gao

Meng²,

Xue³

et al. 2022

Front. Pharmacol.

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Type 2 diabetes mellitus (T2DM) occurs that cannot effectively use the insulin. Insulin Resistance (IR) is a significant characteristic of T2DM which is also an essential treatment target in blood glucose regulation to prevent T2DM and its complications. Bile acids (BAs) are one group of bioactive metabolites synthesized from cholesterol in liver. BAs play an important role in mutualistic symbiosis between host and gut microbiota. It is shown that T2DM is associated with altered bile acid metabolism which can be regulated by gut microbiota. Simultaneously, BAs also reshape gut microbiota and improve IR and T2DM in the bidirectional communications of the gut-liver axis. This article reviewed the findings on the interaction between BAs and gut microbiota in improving T2DM, which focused on gut microbiota and its debinding function and BAs regulated gut microbiota through FXR/TGR5. Meanwhile, BAs and their derivatives that are effective for improving T2DM and other treatments based on bile acid metabolism were also summarized. This review highlighted that BAs play a critical role in the glucose metabolism and may serve as therapeutic targets in T2DM, providing a reference for discovering and screening novel therapeutic drugs.

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Lithocholic acid inhibits dendritic cell activation by reducing intracellular glutathione via TGR5 signaling

Cited by 18 publications

References 55 publications

Patchouli alcohol inhibits GPBAR1-mediated cell proliferation, apoptosis, migration, and invasion in prostate cancer

Patchouli alcohol inhibits GPBAR1-mediated cell proliferation, apoptosis, migration, and invasion in prostate cancer

The role of bile acid receptor TGR5 in regulating inflammatory signalling

Bile acids-gut microbiota crosstalk contributes to the improvement of type 2 diabetes mellitus

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