Abstract
Many anti-inflammatory agents have been exploited for the treatment of inflammatory diseases by targeting the most potent proinflammatory cytokines including tumor necrosis factor (TNF) and interleukin-1 (IL-1). Theoretically, simultaneous neutralization or blocking two important inflammatory mediators might achieve a synergistic therapeutic effect. A recombinant fusion protein, TNFR2-Fc-IL-1ra (TFI), was developed as bifunctional inflammatory inhibitor. TFI was able to strongly neutralize TNF activity and to antagonize IL-1 receptor in the cell binding inhibition assays, suggesting that TFI could be used as a bifunctional ligand with enhanced anti-inflammatory effect.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blotting, Western
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CHO Cells
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Cell Proliferation / drug effects
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Cells, Cultured
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Cricetulus
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Fibroblasts / cytology
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Fibroblasts / drug effects
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Fibroblasts / metabolism
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Humans
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Immunoglobulin Fc Fragments / genetics
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Immunoglobulin Fc Fragments / metabolism*
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Interleukin 1 Receptor Antagonist Protein / antagonists & inhibitors
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Interleukin 1 Receptor Antagonist Protein / genetics
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Interleukin 1 Receptor Antagonist Protein / metabolism*
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Interleukin-1 / pharmacology*
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Mice
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Neutralization Tests / methods*
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Plasmids / genetics
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Receptors, Tumor Necrosis Factor, Type II / antagonists & inhibitors
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Receptors, Tumor Necrosis Factor, Type II / genetics
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Receptors, Tumor Necrosis Factor, Type II / metabolism*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / pharmacology*
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Tumor Necrosis Factor-alpha / pharmacology*
Substances
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Immunoglobulin Fc Fragments
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Interleukin 1 Receptor Antagonist Protein
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Interleukin-1
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Receptors, Tumor Necrosis Factor, Type II
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Recombinant Fusion Proteins
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Tumor Necrosis Factor-alpha