PSTPIP2 Inhibits the Inflammatory Response and Proliferation of Fibroblast-Like Synoviocytes in vitro.

Yao Yao,Cheng Huang,Haixia Yu,Jun Li,Xiaoming Meng,Xiaofeng Li,Qingqing Xu,Yaru Liu

doi:10.3389/fphar.2018.01432

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease and its pathogenesis remains unclear. Fibroblast-like synoviocytes (FLSs) play an important role in the pathogenesis of RA. Proline-serine-threonine phosphatase interacting protein 2 (PSTPIP2) is an adaptor protein, which is associated with auto-inflammatory disease. In this study, we selected adjuvant-induced arthritis (AIA) as animal model to study the role of PSTPIP2 in FLSs. We found that the expression of PSTPIP2 was significantly down-regulated in synovial tissues and FLSs of AIA rat compared with normal group. And overexpression of PSTPIP2 could inhibit the proliferation and inflammatory response of FLSs. Moreover, the proliferation and inflammatory response of FLSs were promoted with PSTPIP2 silencing treatment. In terms of mechanism, we found that the expression of PSTPIP2 was closely related to NF-κB signaling pathway. Overall, our results suggested that PSTPIP2 inhibits the proliferation and inflammatory response of FLSs, which might be closely related to NF-κB signaling pathway.

Highlights

Rheumatoid arthritis (RA) is a chronic inflammatory and autoimmune disease (Miossec, 2013; Kriegsmann et al, 2016; Mastroleo, 2016)
These results indicated that overexpression of Proline-serine-threonine phosphatase interacting protein 2 (PSTPIP2) could suppress the inflammatory response of Fibroblast-like synoviocytes (FLSs)
We analyzed the effect of PSTPIP2 on the inflammatory response and proliferation of FLSs in experimental arthritis model in vitro

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic inflammatory and autoimmune disease (Miossec, 2013; Kriegsmann et al, 2016; Mastroleo, 2016). The development of new treatments targeting specific pathophysiological factors would generate crucial understanding toward the complex mechanisms underlying RA, and produce improved outcomes. Fibroblast-like synoviocytes (FLSs) play an important role in the development of synovitis and joint damage in RA (Miao et al, 2013). Activated FLSs in RA exhibit tumor-like behavior such as invasion, migration, and hyperproliferation, but no similar phenomena are observed in other fibroblasts (Bottini and Firestein, 2013). Hyperproliferative FLSs release large amounts of proinflammatory cytokines, leading to destruction of bone and cartilage (Tolboom et al, 2002; Duarte, 2015; Mu et al, 2016; Zou et al, 2016).

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