Abstract
Tumor-necrosis factor-alpha (TNF-alpha) is a potent proinflammtory cytokine and a key molecule in the pathogenesis of rheumatoid arthritis (RA). Retinoic acid-inducible gene-I (RIG-I) is a DExH box protein, which is known to play a role in the inflammatory and immune reactions. We previously reported about potential involvement of RIG-I in synovial inflammation in RA. In the present study, we demonstrated the expression of RIG-I in fibroblast-like synoviocytes stimulated with TNF-alpha. RNA interference against interferon (IFN)-beta abolished the TNF-alpha-induced RIG-I expression. In addition, knockdown of RIG-I partially inhibited the TNF-alpha-induced expression of CC chemokine ligand (CCL) 5, a chemokine with chemotactic activity toward lymphocytes and monocytes. These findings suggest that the TNF-alpha/IFN-beta/RIG-I/CCL5 pathway may be involved in the pathogenesis of synovial inflammation in RA.
MeSH terms
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Arthritis, Rheumatoid / genetics
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Arthritis, Rheumatoid / immunology*
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Arthritis, Rheumatoid / pathology
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Calcium-Binding Proteins / immunology
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Calcium-Binding Proteins / metabolism
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Cells, Cultured
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Chemokine CCL5 / genetics
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Chemokine CCL5 / immunology
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Chemokine CCL5 / metabolism
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Feedback, Physiological / genetics
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Feedback, Physiological / immunology
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Fibroblasts / immunology
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Fibroblasts / metabolism*
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Fibroblasts / pathology
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Humans
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Interferon-beta / genetics
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Interferon-beta / immunology
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Interferon-beta / metabolism
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RNA Interference / immunology
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RNA, Small Interfering
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Receptors, Retinoic Acid / genetics
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Receptors, Retinoic Acid / immunology
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Receptors, Retinoic Acid / metabolism*
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S100 Calcium-Binding Protein A4
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Signal Transduction / immunology
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Synovial Fluid / immunology
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Synovial Fluid / metabolism*
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Transcriptional Activation / immunology
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Tumor Necrosis Factor-alpha / immunology*
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Tumor Necrosis Factor-alpha / metabolism
Substances
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CCL5 protein, human
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Calcium-Binding Proteins
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Chemokine CCL5
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PLAAT4 protein, human
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RNA, Small Interfering
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Receptors, Retinoic Acid
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S100 Calcium-Binding Protein A4
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Tumor Necrosis Factor-alpha
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S100A4 protein, human
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Interferon-beta