| First Author | Li ZY | Year | 2019 |
| Journal | Mol Med Rep | Volume | 20 |
| Issue | 5 | Pages | 4540-4550 |
| PubMed ID | 31702035 | Mgi Jnum | J:290086 |
| Mgi Id | MGI:6435267 | Doi | 10.3892/mmr.2019.10711 |
| Citation | Li ZY, et al. (2019) Activation of TGR5 alleviates inflammation in rheumatoid arthritis peripheral blood mononuclear cells and in mice with collagen IIinduced arthritis. Mol Med Rep 20(5):4540-4550 |
| abstractText | Rheumatoid arthritis (RA) is characterized by chronic in fl ammatory synovitis resulting in progressive joint destruction. Persistent synovial inflammation is induced by activation of various in fl ammatory cells. Gproteincoupled bile acid receptor 1 (TGR5) is a Gproteincoupled receptor activated by various bile acids, which has been reported to act as a key adaptor in regulating various signaling pathways involved in inflammatory responses and a diverse array of physiological processes, including bile acid synthesis, lipid and carbohydrate metabolism, carcinogenesis, immunity and inflammation. In the present study, TGR5 expression was detected in RA peripheral blood mononuclear cells (PBMCs), and its association with clinical disease activity, histological synovitis severity and radiological joint destruction was analyzed. Subsequently, the role and potential underlying mechanisms of TGR5 in the PBMCs of patients with RA and mice with collagen IIinduced arthritis (CIA) were investigated. PBMCs were obtained from 50 patients with RA and 40 healthy controls (HCs). The mRNA and protein expression levels of TGR5 were detected in PBMCs via reverse transcriptionquantitative polymerase chain reaction (RTqPCR) and immunofluorescence staining, respectively. Additionally, the levels of proinflammatory cytokines were analyzed by RTqPCR and enzymelinked immunosorbent assay (ELISA). The activation of nuclear factorkappaB (NFkappaB) and IkappaB kinase a was determined via western blot analysis. The antiarthritic and antiinflammatory effects of LCA on mice with CIA were then investigated. The arthritis score was assessed, and the protein levels of proinflammatory cytokines in the plasma of mice were detected via ELISA. TGR5 mRNA expression was significantly downregulated in the PBMCs of patients with RA compared with in those of the HCs (0.53+/-0.58 for patients vs. 1.49+/-0.83 for HCs; P<0.001); similar findings were observed at the protein level. The mRNA expression levels of TGR5 in the PBMCs of patients with RA with a high 28Joint Disease Activity Score (DAS28) were significantly decreased compared with in patients with a low DAS28 (0.81+/-0.65 for low score vs. 0.35+/-0.46 for high score; P=0.002). Furthermore, TGR5 expression was significantly correlated with the levels of Creactive protein (r=0.429; P=0.002) and the DAS28 (r=0.383; P=0.006). RTqPCR and ELISA analyses indicated that lithocholic acid (LCA, 10 mg/kg/day) attenuated lipopolysaccharideinduced proinflammatory cytokine production via inhibition of NFkappaB activity in the PBMCs of patients with RA. In addition, the arthritis score was significantly decreased in LCAtreated CIA mice compared with in nontreated CIA mice. The increased production of tumor necrosis factoralpha, interleukin (IL)1beta, IL6 and IL8 was significantly reduced in the plasma of LCAtreated CIA mice compared with the control. In conclusion, TGR5 may contribute to the inflammation of PBMCs in patients with RA and mice with CIA. |
