ABSTRACT
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ABSTRACT
Objective: To investigate the expression and function of plexin A1, a transmembrane protein involving cell survival and cell-to cell interaction, in the rheumatoid synoviocytes. Methods: Immunohistochemical staining using anti-plexin A1 antibody was performed in the synovium of rheumatoid arthritis (RA) patients. The plexin A1 expression in cultured fibroblast-like synovioytes (FLS) was also examined by Western blot analysis and immunocytochemistry. Cell viability was determined by CCK-8 assay. Deficiency of plexin A1 was established by the method of short interfering RNA (siRNA). The productions of interleukin-6 (IL-6) and monocytes chemotactic protein-1 (MCP-1) were measured in culture supernatants by ELISA. Results: Plexin A1 was highly expressed in the lining layer of synovium and cultured FLS of RA patients. In RA FLS, basal expression of plexin A1 was higher than osteoarthritis FLS. On immunocytochemical staining, plexin A1 was co-expressed with neuropilin-1 in RA FLS. Semaphorin 3A (10 to 200 ng/mL), a specific ligand for neuropilin-1/plexin A1 complex, did not affect viability of RA FLS. The down regulation of plexin A1 mRNA by siRNA did not cause cell death, either. Co-culture of FLS with RA T cells, isolated from peripheral blood or synovial fluid, caused an increase in the productions of IL-6 and MCP-1 from FLS, but which were blocked by down-regulating plexin A1 transcripts using siRNA method. Conclusion: These data suggest that enhanced expression of plexin A1 in RA FLS may elicit over-production of IL-6 and MCP-1, and thereby contribute to perpetuation of chronic inflammation in RA.