Abstract
Recombinant human interleukin-4 (rhIL-4) and rhIL-1 alpha each produced a rapid down-modulation of tumour necrosis factor receptor (TNFR) on rheumatoid synovial fibroblasts (RSF) in vitro. This was associated with a staurosporine-resistant increase in p55 soluble TNFR levels, in culture media, suggesting that down-modulation was due to enhanced receptor shedding via a protein kinase C-independent mechanism. Pretreatment with rhIL-4 reduced the subsequent tumour necrosis factor alpha (TNF alpha) stimulation of prostaglandin E (PGE) and matrix metalloproteinase-3 (MMP-3) production by RSF. Thus, the potential anti-synovial monokine properties of rhIL-4 are not confined to inhibiting monokine production but also include the ability to interfere with their action on cells that constitute a substantial proportion of the rheumatoid synovium.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkaloids / pharmacology
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Antigens, CD*
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Arthritis, Rheumatoid / immunology*
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Binding, Competitive / drug effects
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Cells, Cultured
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Down-Regulation / drug effects
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Fibroblasts / immunology
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Humans
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Interleukin-4 / immunology
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Interleukin-4 / pharmacology*
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Monokines / biosynthesis
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Monokines / drug effects
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Protein Kinase C / antagonists & inhibitors
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Receptors, Tumor Necrosis Factor / drug effects*
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Receptors, Tumor Necrosis Factor, Type I
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Recombinant Proteins / pharmacology
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Staurosporine
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Synovial Membrane / immunology*
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Tumor Necrosis Factor-alpha / biosynthesis
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Tumor Necrosis Factor-alpha / drug effects*
Substances
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Alkaloids
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Antigens, CD
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Monokines
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Receptors, Tumor Necrosis Factor
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Receptors, Tumor Necrosis Factor, Type I
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Recombinant Proteins
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Tumor Necrosis Factor-alpha
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Interleukin-4
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Protein Kinase C
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Staurosporine