The Role Of C-reactive Protein On The Pathogenesis Of Rheumatoid Arthritis

Objective To study the role of C-reactive protein on the pathogenesis of rheumatoid arthritis.Methods Culture RA and normal synovial fibroblasts in vitro. The expression of CRP and its receptor CD32, CD64 mRNA in RA and normal synovial fibroblasts were measured by qRT-PCR. The expression of CD32,CD64 and CRP protein RA and normal synovial fibroblasts were measured by immunohistochemistry and western blot.RA and normal synovial fibroblasts were incubated by CRP, the expression of inflammatory cytokines and MMP-3 mRNA were measured by qRT-PCR. The level of phosphorylation p65 in RA synovial fibroblasts were measured by western blot.The RA synovial fibroblasts were incubated by CRP combine with CD32 inhibitor or CRP combine with NF-κB inhibitor, the expression of inflammatory cytokines and MMP-3 mRNA were measured by qRT-PCR.The RA synovial fibroblasts were incubated by IL-1β or TNF-α,the expression of CRP mRNA were measured by qRT-PCR.The RA synovial fibroblasts were incubated by IL-1β combine with NF-κB inhibitor or TNF-α combine with NF-KB inhibitor, the expression of CRP mRNA were measured by qRT-PCR.Results The expression of CRP and its receptor CD32,CD64 mRNA and protein were significantly higher in RA synovial fibroblasts than normal synovial fibroblasts. The RA and normal synovial fibroblasts were incubated by CRP, the expression of inflammatory cytokines and MMP-3 mRNA were significantly higher in RA synovial fibroblasts than control and the RA synovial fibroblasts level of phosphorylation p65 were increased. The expression of inflammatory cytokines and MMP-3 mRNA were significantly decreased with incubated by CRP combine with CD32 inhibitor or CRP combine with NF-κB inhibitor in RA synovial fibroblasts. The RA synovial fibroblasts were incubated by IL-1βand TNF-α, the expression of CRP mRNA were significantly higher than control. The expression of CRP mRNA were significantly decreased with incubated by IL-1βcombine with NF-κB inhibitor or TNF-α combine with NF-κB inhibitor.Conclusion CRP may be the pathogenesis of RA by stimulating the generation of inflammatory cytokines and MMP-3, the process achieved via the CD32 and CD64 mediated activation of NF-κB signalling pathways. IL-1β and TNF-α via activation of NF-κB signalling pathways stimulates the generation of CRP.CRP is not only just a biomarker but also involved in the pathogenesis of RA.