Role In Pathogenesis Of RA Research Articles

A critical role of E2F transcription factor 2 in proinflammatory cytokines-dependent proliferation and invasiveness of fibroblast-like synoviocytes in rheumatoid Arthritis

As a transcription factor, E2F2 participates in regulation of numerous genes. To investigate the role and mechnism of E2F2 in RA, expression of E2F2 in synovial tissue was detected. Proliferation, invasion, and secretion of inflammatory cytokines were measured after E2F2 was knocked-down in RASFs by siRNA transfection. Induction of TNF-α, IL-6, and LPS on expression and nuclear translocation of E2F2, and signal pathways involved in the process were tested. ChIP was used to investigate direct binding of NF-кB to the promoter of E2F2, and E2F2 to the promoter of IL-6. The correlation between mRNA levels of E2F2 and IL-6 or TNF-α in secreted in supernatant of RASFs were also investigated. As a result, silencing E2F2 could inhibit the proliferation and invasion of RASFs. LPS, IL-6 can stimulate the expression of E2F2 in RASFs both via the NF-кB pathway, while TNF-α via the ERK pathway. TNF-α can facilitate the nuclear translocation of E2F2 and TNF-α can bind to promoter of E2F2, and then E2F2 can bind to the promoter of IL-6 directly. Significant correlations was found between levels of E2F2 and IL-6/TNF-α in synoviocytes of RA patients. Our findings indicate that E2F2 may play an important role in pathogenesis of RA.

Evaluation of galectin-3 genetic variants and lipid profile in RA patients in North Indian population

Results The genotypic distribution of +191(A/C) showed significant differences between patients and controls (odds ratio = 1.9552, 95% CI = 1.0461-3.6542, p 0.05 ). RA patients were found to be dyslipidemic as indicated by the significantly higher atherogenic index as compared to controls (p<0.01). Conclusion Galectin-3 may play an important role in pathogenesis of RA.

Anti-citrullinated protein antibodies: role in pathogenesis of RA and potential as a diagnostic tool

Rheumatoid arthritis is an autoimmune disorder which involves inflammation of the synovial tissue, leading to synovial proliferation, bone erosion and ultimately joint disability. It is a complex disorder, and the proper etiology is still unknown. Both environmental and genetic factors are responsible for the development of rheumatoid arthritis. Clinically, the disease is generally diagnosed by the presence of auto-antibodies like rheumatoid factor. But these are not specifically associated with rheumatoid arthritis. These are also present in patients with other autoimmune disorders and also in healthy persons. Citrullinated epitopes are shown to be more specific for rheumatoid arthritis. Citrullination normally occurs in cells undergoing apoptosis, and hence, citrullinated proteins are cleared from body and not encountered by immune system. However, in rheumatoid arthritis patients, these are not cleared. Anti-citrullinated protein antibodies are detectable in patients at risk of rheumatoid arthritis long before the onset of the disease. The concentration of which normally increases as the disease progress. Hence, these are important for diagnosis of rheumatoid arthritis. This review is focused on the importance of anti-citrullinated protein antibodies in disease pathogenesis and its importance in the diagnosis of rheumatoid arthritis.