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KMID : 0388220070140040322
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Journal of the Korean Rheumatism Association
2007 Volume.14 No. 4 p.322 ~ p.330
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The Blocking of TNF-alpha by RNA Interference and Its Influence on Synovial Fibroblast and Chondrocytes
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Kim Hyun-Ah
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Abstract
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Objective: Small interfering RNA (siRNA) triggers RNA interference in mammalian somatic cells. TNF-? is a proinflammatory cytokine implicated in the pathogenesis of inflammatory arthritis including rheumatoid arthritis (RA). This study was to use TNF receptor 1 (TNFRI)- specific siRNA to inhibit the TNF-? mediated signaling in RA fibroblast like synoviocytes (FLS) and chondrocytes. Methods: TNFRI specific siRNA was produced by targeting 3 nucleotide sequences at 474∼494, 562∼582 and 668∼688. Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot were performed to optimize the silencing effects of TNFRI siRNA in cultured FLS and chondrocytes. The inhibition of TNF-? mediated signaling was determined by ELISA assay of metalloproteinase 1 secretion induced by TNF-?. Results: The TNFRI siRNA inhibited the expression of TNFRI mRNA and protein in both RA FLS and chondrocytes. MMP-1 secretion induced by TNF-? was significantly downregulated by TNFRI siRNA. Conclusion: TNFRI siRNA can inhibit the expression and signaling downstream of TNFRI in both RA FLS and chondrocytes efficiently. This suggests that RNA interference technique by siRNA could be considered as a potential therapeutic target for RA.
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KEYWORD
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Rheumatoid arthritis, siRNA, TNF-?, TNF receptor 1, Metalloproteinasepocomplementemia
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