Session Type: Abstract Submissions (ACR)
Background/Purpose Class A scavenger receptor (SR-A/CD204), mainly expressed on macrophages, plays an important role in the pathogenesis of atherosclerosis and in the pattern recognition of pathogen infection. However, its role in rheumatoid arthritis (RA) has not been defined. The aim of this study was to reveal the expression of SR-A in synovial fibroblasts (RASF) and its impact on synovial inflammation.
Methods Immunohistochemistry (IHC) was performed to detect the expression of SR-A in the synovial tissues from RA and osteoarthritis (OA) patients. The expression of SR-A in RASF was demonstrated by both qPCR and western blot. To reveal the effects of SR-A on synovial inflammation, RASF were treated with either recombinant SR-A protein or SR-A specific siRNA. Then, the expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-8) and MMPs (MMP-1, MMP-3, and MMP-9) were determined by real-time PCR and ELISA. Accordingly, the activation of the MAPKs and NF-κB signaling pathways was evaluated by western blot when SR-A was silenced.
Results The level of SR-A was higher in the synovial tissues from RA patients than those from OA patients. Moreover, we for the first time demonstrated that SR-A was expressed in RASF. SR-A protein stimulated pro-inflammatory cytokine and MMP expression in RASF. On the contrary, knocking down SR-A by specific siRNA suppressed the expression of these factors, with dampened activation of the ERK, JNK, p38 and NF-κB signaling pathways.
Conclusion SR-A exacerbated synovial inflammation and cartilage erosion in RA. Targeting SR-A might provide novel therapeutic strategies for overcoming this stubborn disease.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/class-a-scavenger-receptor%ef%bc%88sr-a%ef%bc%89exacerbated-synovial-fibroblasts-mediated-inflammation-in-rheumatoid-arthritis/