Abstract
Rheumatoid arthritis (RA) is characterized by inflammatory cell infiltration, fibroblast-like synoviocytes (FLS) invasive proliferation, and joint destruction. Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that induces immune activation. In this study, we examined whether cGAS plays a role in RA FLS. In this study, cGAS was overexpressed in RA-FLS compared with OA FLS. TNFα stimulation induced cGAS expression in RA FLS. Overexpression of cGAS promoted the proliferation and knockdown of cGAS inhibited the proliferation of RA FLS. cGAS overexpression enhanced the production of proinflammatory cytokines and matrix metalloproteinases (MMPs) as well as AKT and ERK phosphorylation in TNFα-stimulated FLS. In contrast, cGAS silencing inhibited production of proinflammatory cytokines and matrix metalloproteinases (MMPs) as well as AKT and ERK phosphorylation in TNFα-stimulated FLS. These results suggest that cGAS activates the AKT and ERK pathways to promote the inflammatory response of RA FLS, and the development of strategies targeting cGAS may have therapeutic potential for human RA.
Highlights
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by proliferative synovitis, hyperplasia of the synovial tissues, and destruction of cartilage and bone
The results showed that Fibroblast-like synoviocytes (FLS) infected with cyclic GMP-AMP synthase (cGAS)-vector produced significantly higher amounts of IL-1β, IL-6, matrix metalloproteinases (MMPs)-1, and MMP-3 than did FLS infected with control (Figure 4(a), P < 0.01) when exposed to TNFα stimulation for 30 min
We found that cGAS was overexpressed in RA-FLS compared with OA FLS
Summary
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by proliferative synovitis, hyperplasia of the synovial tissues, and destruction of cartilage and bone. The activated FLS proliferation in RA joints and their secretions such as proinflammatory cytokines and matrix metalloproteinases (MMPs) play pivotal roles in the development of synovial hyperplasia, sustained inflammation, and joint destruction in arthritic joints [3]. Several studies have recently revealed a role for type I interferons (IFNs) in the pathogenesis of RA patients [4]. Genetic variants associated with type I IFN pathway have been linked with RA development, as well as with clinical features [5, 6]. Recent studies have implicated the key role of cGAS in autoimmune disease in the mouse model of AicardiGoutieres syndrome and in the innate and adaptive immune responses in features of human lupus [9,10,11]. We explored whether cGAS is involved in the pathogenesis of human RA via affecting RA-FLS
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
