p53 in fibroblast-like synoviocytes can regulate T helper cell functions in patients with active rheumatoid arthritis

Background p53 is a tumor suppressor and plays a key role in regulating cell hyperplasia, repairing DNA and inducing apoptosis. This study was to investigate p53 expression in fibroblast-like synoviocytes (FLS) and its effect on CD4(+) T lymphocytes from patients with active rheumatoid arthritis (RA). Methods Human FLS were transfected with p53 siRNA and cocultured with CD4(+) T lymphocytes from patients with active RA. The expressions of osteoprotegerin and interleukin (IL)-6 were detected in p53 siRNA and scramble siRNA-transfected FLS. In addition, protein levels of interferon (IFN)-gamma gamma, IL-17, IL-4 and CD25 as well as mRNAs of IFN-gamma, retinoic acid-related orphan receptor (ROR)-gamma t, IL-17 and Foxp3 in cocultured CD4(+) T lymphocytes were also measured. Results IL-6 decreased in p53-knockdown FLS while osteoprotegerin expression was not altered. FLS with p53 deletion significantly increased the production of IL-17 and IFN-gamma by CD4(+) T cells and upregulated Foxp3 mRNA expression without effects on the proportion of CD4(+)CD25(high) T lymphocytes. Conclusion p53 in FLS might regulate Th1 and Th17 functions in patients with RA and participate in the pathogenesis of RA. Chin Med J2011;124(3):364-368