PTEN negatively regulates the expression of pro-inflammatory cytokines and chemokines of fibroblast-like synoviocytes in adjuvant-induced arthritis.

Rheumatoid arthritis (RA) is characterized by tumor-like expansion of the synovium and the subsequent destruction of adjacent articular cartilage and bone. The latest studies proved phosphatase and tension homolog deleted on chromosome 10 (PTEN) might contribute to the surviving, proliferation and pro-inflammatory cytokines in RA. The purpose of this study was to explore the function and underlying mechanisms of PTEN in RA pro-inflammatory cytokines and chemokines of fibroblast-like synoviocytes (FLSs). Increased level of PTEN was observed in adjuvant-induced arthritis (AIA) FLSs in comparison to normal rats. Increased concentrations of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), chemokines (CCL-2 and CCL-3), VCAM-1 and VEGF-α expression were observed in FLSs with PTEN inhibitor bpv or PTEN-RNAi. Moreover, co-incubation FLSs with overexpression vector with PTEN-GV141 reduced the expression of pro-inflammatory cytokines, chemokines, VCAM-1 and VEGF-α in AIA. Interestingly, we also found DNA methylation could regulate PTEN expression and activation of AKT signaling was with a change of PTEN. Altogether, our findings in the present study suggested that PTEN might play a pivotal role during pro-inflammatory cytokines and chemokines of FLSs through activation of AKT signaling pathway. In addition, PTEN expression may be regulated by DNA methylation in the pathogenesis of AIA.