Taurolithocholic acid but not tauroursodeoxycholic acid rescues phagocytosis activity of bone marrow‐derived macrophages under inflammatory stress

Wu, Siyu; Romero‐Ramírez, Lorenzo; Mey, Jörg

doi:10.1002/jcp.30619

Cited by 9 publications

(3 citation statements)

References 75 publications

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“…To define the role of TGR5 in mouse Leydig cells, we explored its impact on endocrine function by measuring the production of testosterone using the mLTC1 cell line. As TGR5 modulates the protein kinase (PKA) pathway [ 10 , 14 , 15 ], which is a fast second cellular messenger, we decided to analyze the effect of TGR5 activation in short-time experiments. Treatment of mLTC1 cells with the TGR5 agonist INT-777 for 3 h resulted in a significant decrease in intracellular testosterone levels compared to vehicle-treated cells, while this effect was not observed after 6 h ( Figure 2 A).…”

Section: Resultsmentioning

confidence: 99%

Identification of the Role of TGR5 in the Regulation of Leydig Cell Homeostasis

Holota

Haze

Martinot

et al. 2022

IJMS

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Understanding the regulation of the testicular endocrine function leading to testosterone production is a major objective as the alteration of endocrine function is associated with the development of many diseases such as infertility. In the last decades, it has been demonstrated that several endogenous molecules regulate the steroidogenic pathway. Among them, bile acids have recently emerged as local regulators of testicular physiology and particularly endocrine function. Bile acids act through the nuclear receptor FXRα (Farnesoid-X-receptor alpha; NR1H4) and the G-protein-coupled bile acid receptor (GPBAR-1; TGR5). While FXRα has been demonstrated to regulate testosterone synthesis within Leydig cells, no data are available regarding TGR5. Here, we investigated the potential role of TGR5 within Leydig cells using cell culture approaches combined with pharmacological exposure to the TGR5 agonist INT-777. The data show that activation of TGR5 results in a decrease in testosterone levels. TGR5 acts through the PKA pathway to regulate steroidogenesis. In addition, our data show that TGR5 activation leads to an increase in cholesterol ester levels. This suggests that altered lipid homeostasis may be a mechanism explaining the TGR5-induced decrease in testosterone levels. In conclusion, the present work highlights the impact of the TGR5 signaling pathway on testosterone production and reinforces the links between bile acid signaling pathways and the testicular endocrine function. The testicular bile acid pathways need to be further explored to increase our knowledge of pathologies associated with impaired testicular endocrine function, such as fertility disorders.

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Section: Resultsmentioning

confidence: 99%

Identification of the Role of TGR5 in the Regulation of Leydig Cell Homeostasis

Holota

Haze

Martinot

et al. 2022

IJMS

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“…At this post-acute stage, the inflammatory reaction, though already decreasing, is still a prevailing process and typically continues into a chronic stage. This implies not only cytotoxic effects but may also compromise the phagocytosis ability of macrophages [30]. We hypothesize that the injected bmSCs are beneficial for reducing these pathological processes, because anti-inflammatory effects of these cells were observed in previous experiments, which included analysis in the next days after treatment [12,14].…”

Section: Mechanism Of Actionmentioning

confidence: 91%

Improved Efficacy of Delayed Treatment with Human Bone Marrow-Derived Stromal Cells Evaluated in Rats with Spinal Cord Injury

Aguado-Garrido,

García-Rama,

Romero-Ramírez

et al. 2024

IJMS

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The treatment of spinal cord injury (SCI) with uncultivated human bone marrow-derived stromal cells (bmSCs) prepared by negative selection has been proposed to be therapeutically superior to treatment with stem cells that were expanded in vitro. To explore their use in clinical trials, we studied the functional effects of delayed application at 7 days after SCI by testing different doses of bmSCs. Spinal cord contusion injury was induced in adult male Wistar rats at the thoracic level T9. Human bmSCs were prepared by negative selection without expansion in vitro (NeuroCellsTM). Treatment consisted of one 150 µL injection into the cisterna magna containing 0.5 or 2.5 million fresh bmSCs or 2.5 million bmSCs. The recovery of motor functions was evaluated during a surveillance period of six weeks (6 W), during which spinal cords were assessed histologically. Treatment resulted in a significant, dose-dependent therapeutic effect on the recovery of motor performance. The histological analysis revealed a lower degree of axonal degeneration and better survival of neurons and oligodendrocytes in bmSCs treated rats. Our results support delayed intrathecal application of bmSCs prepared by negative selection without expansion in vitro as a treatment of SCI.

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“…The primary and secondary BAs exist in dynamic equilibrium to regulate host physiology. For instance, in a TGR5‐dependent manner, both primary and secondary BAs suppress LPS induction of pro‐inflammatory cytokines in macrophages 83 . INT‐777, a TGR5‐specific semisynthetic bile acid, inhibited the formation of foam cells by the decrease in LDL uptake 84 …”

Section: The Impacts Of Gm On the Immunopathology Of Atherosclerosismentioning

confidence: 99%

Role of gut microbiota in the immunopathology of atherosclerosis: Focus on immune cells

et al. 2022

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Gut microbiota (GM) plays important roles in multiple organ function, homeostasis and several diseases. More recently, increasing evidences have suggested that the compositional and functional alterations of GM play a crucial role in the accumulation of foam cells and the formation of atherosclerotic plaque in atherosclerosis. In particular, the effects of bacterial components and metabolites on innate and adaptive immune cells have been explored as the underlying mechanisms. Understanding the effects of GM and metabolites on immunoregulation is important for clinical therapy for atherosclerosis. Herein, we summarize the potential role of the GM (such as bacterial components lipopolysaccharide and peptidoglycan) and GM‐derived metabolites (such as short‐chain fatty acids, trimethylamine N‐oxide and bile acids) in the immunopathology of atherosclerosis. Based on that, we further discuss the anti‐atherosclerotic effects of GM‐directed dietary bioactive factors such as dietary fibres, dietary polyphenols and probiotics. Because of drug‐induced adverse events in anti‐inflammatory therapies, personalized dietary interventions would be potential therapies for atherosclerosis, and the interactions between GM‐derived products and immune cells should be studied further.

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Taurolithocholic acid but not tauroursodeoxycholic acid rescues phagocytosis activity of bone marrow‐derived macrophages under inflammatory stress

Cited by 9 publications

References 75 publications

Identification of the Role of TGR5 in the Regulation of Leydig Cell Homeostasis

Identification of the Role of TGR5 in the Regulation of Leydig Cell Homeostasis

Improved Efficacy of Delayed Treatment with Human Bone Marrow-Derived Stromal Cells Evaluated in Rats with Spinal Cord Injury

Role of gut microbiota in the immunopathology of atherosclerosis: Focus on immune cells

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