TRAF2 and cIAP2 involve in TWEAK-induced MMP-9 production in fibroblast-like synoviocytes

Excerpt

Rheumatoid arthritis (RA) is a chronic disease that causes synovial inflammation and progressive destruction of the cartilage and bone of diarthrodial joints. Fibroblast-like synoviocytes (FLS) play an essential role as effector cells in joint destruction through the production of matrix metalloproteases (MMPs), mainly gelatinases. Tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a TNF ligand superfamily member that is known as a novel arthritogenic mediator [1]. TWEAK can induce MMP-9 production by FLS via its receptor, fibroblast growth factor inducible 14 (Fn14), which indicates that the TWEAK/Fn14 pathway may directly promote bone and cartilage damage [2]. Fn14 has been shown to bind TNF receptor-associated factor 2 (TRAF2) and TRAF 1, 3, and 5 in a yeast two-hybrid screen [3]. Recent evidence also suggests that cellular inhibitor of apoptosis 1 (cIAP1) and clAP2 proteins through their interaction with TRAF2 protein mediates the TNF-α-induced activation of NF-kB [4]. …