Abstract
The fibroblasts stimulated by cytokines released the chemokine and recruited the infiltrating cells, including eosinophils, that play a key role in the pathogenesis of airway disease. We established the human fibroblast lines showing high Syk expression and the lines showing low Syk expression from pieces of nasal polyp. IL-1 induces the interaction of TNFR-associated factor (TRAF) 6 with IL-1R-associated kinase, which is rapidly recruited to the IL-1R after IL-1 induction, whereas TRAF2 participates in TNF-alpha-signaling. In the present study, we found that Syk played a different role in IL-1- and TNF-alpha-induced chemokine production through a signaling complex involving Syk and TRAF6. Overexpression of wild-type Syk by gene transfer enhanced RANTES production from nasal fibroblasts stimulated with IL-1. The decrease of Syk expression by the administration of Syk antisense inhibited RANTES production in response to IL-1. However, the change of Syk expression did not affect RANTES production by TNF-alpha stimulation. We concluded that Syk is required for the IL-1-induced chemokine production through the association with TRAF-6 in fibroblasts of nasal polyps.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line
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Chemokine CCL5 / biosynthesis*
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Enzyme Precursors / antagonists & inhibitors
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Enzyme Precursors / biosynthesis
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Enzyme Precursors / genetics
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Enzyme Precursors / physiology*
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Fibroblasts / enzymology*
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Fibroblasts / immunology*
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Fibroblasts / metabolism
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Genetic Vectors / immunology
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Humans
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I-kappa B Proteins / metabolism
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Interleukin-1 / physiology*
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Intracellular Signaling Peptides and Proteins
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases / metabolism
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Nasal Polyps / enzymology
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Nasal Polyps / immunology*
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Nasal Polyps / metabolism
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Oligodeoxyribonucleotides, Antisense / agonists
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Oligodeoxyribonucleotides, Antisense / physiology
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Phosphorylation
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Protein-Tyrosine Kinases / antagonists & inhibitors
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Protein-Tyrosine Kinases / biosynthesis
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / physiology*
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Proteins / metabolism*
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Receptors, Tumor Necrosis Factor / metabolism*
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Syk Kinase
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TNF Receptor-Associated Factor 6
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Transfection
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p38 Mitogen-Activated Protein Kinases
Substances
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Chemokine CCL5
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Enzyme Precursors
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I-kappa B Proteins
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Interleukin-1
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Intracellular Signaling Peptides and Proteins
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Oligodeoxyribonucleotides, Antisense
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Proteins
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Receptors, Tumor Necrosis Factor
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TNF Receptor-Associated Factor 6
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Protein-Tyrosine Kinases
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SYK protein, human
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Syk Kinase
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases