STA ‐21 regulates Th‐17/Treg balance and synovial fibroblasts functions in rheumatoid arthritis

In this study, we tested whether a STAT3 inhibitor, STA-21, can alter Th-17/Treg balance and SF functions in RA. Peripheral blood mononuclear cells (PBMC) and SFs were isolated from 34 RA patients undergoing orthopedic surgery and 15 healthy controls to investigate in  vitro effects of STA-21. The main assays were MTT assay, PI staining, reverse transcription-PCR (RT-PCR), flow cytometric analysis, and ELISA. Results showed that STA-21 reduced the proportion of Th-17 cells and the expression of STAT3 target genes, RORγt, IL-21, and IL-23R involved in Th-17 cell s differentiation while it conversely increased the proportion of Treg cells, which theoretically may result in suppression of inflammation. We found that STAT3 activation and its target gene expression increased in RA-SFs. In addition, results showed that STA-21 can reduce the expression of STAT3 t arget genes related to cell proliferation, apoptosis, and inflammation leading to a decrease in proliferation and conversely increase in apoptosis of RA-SFs. Overall, our findings provide evidence that STA-21 can reduce inflammatory immune processes conducted by T cells and RA-SFs in RA, suggesting that this compound is a suitable option for clinical studies in RA.
Source: International Journal of Rheumatic Diseases - Category: Rheumatology Authors: Tags: ORIGINAL ARTICLE Source Type: research