The effect of taurochenodeoxycholic acid on the glucocorticoid receptormediated PLC-IP3 -calcium pathway in synoviocytes derived from a rat adjuvant arthritis model

Abstract

Taurochenodeoxycholic acid is one of the main active components of the bile acid pool and has important anti-inflammatory and immunomodulatory properties. This study aimed to explore the therapeutic effects and mechanism of action of taurochenodeoxycholic acid in inflammatory arthritis using a rat adjuvant arthritis model. Fibroblast-like synoviocytes were derived from rats with adjuvant arthritis and cultured using the adherent tissue explant method. Western blotting, enzyme-linked immunosorbent assay, and fluorescent probe-based methods were used to detect the effects of taurochenodeoxycholic acid on glucocorticoid receptor expression, phospholipase C protein levels, and inositol trisphosphate and intracellular free Ca2+ concentrations in primary rat fibroblast-like synoviocytes. Taurochenodeoxycholic acid significantly induced the expression of glucocorticoid receptor (P<0.05) and phospholipase C (P<0.05) and enhanced phospholipase C phosphorylation. Moreover, taurochenodeoxycholic acid significantly increased the levels of inositol trisphosphate (P<0.05) and intracellular free Ca2+ concentrations. Our results suggest that taurochenodeoxycholic acid activates the phospholipase C-inositol trisphosphate-Ca2+ signaling pathway by increasing glucocorticoid receptor expression. These findings provide a theoretical foundation for future studies on the molecular mechanisms underlying taurochenodeoxycholic acid-based treatment of adjuvant arthritis. In conclusion, taurochenodeoxycholic acid exerted anti-inflammatory and immunomodulatory effects by enhancing glucocorticoid receptor expression via non-genomic signalling.