Abstract
In this study, we investigated the role of serum amyloid A protein (SAA) in the production of interleukin-6 (IL-6) using rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS). Recombinant SAA stimulation induced the production of pro-inflammatory cytokine, IL-6, from RA-FLS. The signaling events induced by SAA included the activation of the mitogen-activated protein kineases, p38 and JNK1/2 and the activation of nuclear factor-kappa B (NF-kappaB). Inhibitor studies have shown SAA-induced IL-6 production to be down-regulated by NF-kappaB inhibition and partially inhibited by p38 or JNK inhibitors. Our findings demonstrate that SAA is a significant inducer of IL-6, which is critically involved in RA pathogenesis.
MeSH terms
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Arthritis, Rheumatoid / enzymology
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Arthritis, Rheumatoid / genetics
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Arthritis, Rheumatoid / pathology*
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DNA / metabolism
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Fibroblasts / drug effects
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Fibroblasts / enzymology
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Fibroblasts / pathology
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Gene Expression Regulation / drug effects
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Humans
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Interleukin-6 / genetics
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Interleukin-6 / metabolism*
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JNK Mitogen-Activated Protein Kinases / metabolism
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NF-kappa B / antagonists & inhibitors
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Phosphorylation / drug effects
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Protein Binding / drug effects
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptors, Formyl Peptide / genetics
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Receptors, Formyl Peptide / metabolism
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Receptors, Lipoxin / genetics
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Receptors, Lipoxin / metabolism
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Serum Amyloid A Protein / pharmacology*
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Synovial Fluid / cytology*
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Synovial Fluid / drug effects
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Synovial Fluid / enzymology
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Synovial Fluid / metabolism*
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Transcription Factor RelA / metabolism
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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FPR2 protein, human
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Interleukin-6
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NF-kappa B
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RNA, Messenger
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Receptors, Formyl Peptide
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Receptors, Lipoxin
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Serum Amyloid A Protein
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Transcription Factor RelA
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DNA
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JNK Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases