Abstract
IL-33 (or IL-1F11) was recently identified as a ligand for the previously orphaned IL-1 family receptor T1/ST2. Previous studies have established that IL-33 and T1/ST2 exert key functions in Th2 responses. In this study, we demonstrate that IL-33 induces the production of pro-inflammatory mediators in mast cells. IL-33 dose and time-dependently stimulated IL-6 secretion by P815 mastocytoma cells and primary mouse bone marrow-derived mast cells (BMMC). This effect was dependent on T1/ST2 binding. In addition, IL-33 also induced IL-1beta, TNF-alpha, MCP-1, and PGD2 production in BMMC. By RNase protection assay, we demonstrated that IL-33 increased IL-6 and IL-1beta mRNA expression. These effects of IL-33 appeared to occur independently of mast cell degranulation, The results of this study show for the first time that IL-33, a novel member of the IL-1 family of cytokines, stimulates the production of pro-inflammatory mediators by mast cells in addition to its effect on T helper 2 responses. These findings open new perspectives for the treatment of inflammatory diseases by targeting IL-33.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bone Marrow Cells / cytology
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Bone Marrow Cells / immunology
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Bone Marrow Cells / metabolism
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Cell Line
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Chemokine CCL2 / biosynthesis
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Chemokine CCL2 / immunology
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Dose-Response Relationship, Drug
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Inflammation / drug therapy
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Inflammation / immunology
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Inflammation / metabolism
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Inflammation Mediators / immunology*
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Inflammation Mediators / metabolism
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Interleukin-1 Receptor-Like 1 Protein
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Interleukin-1beta / biosynthesis
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Interleukin-1beta / immunology
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Interleukin-33
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Interleukins / immunology
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Interleukins / pharmacology*
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Mast Cells / cytology
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Mast Cells / immunology*
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Mast Cells / metabolism
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Membrane Proteins / immunology
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Membrane Proteins / metabolism
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Mice
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Prostaglandin D2 / biosynthesis
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Prostaglandin D2 / immunology
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Protein Binding / immunology
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Receptors, Interleukin
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Th2 Cells / cytology
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Th2 Cells / immunology
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Time Factors
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Tumor Necrosis Factor-alpha / biosynthesis
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Tumor Necrosis Factor-alpha / immunology
Substances
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Ccl2 protein, mouse
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Chemokine CCL2
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Il1rl1 protein, mouse
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Il33 protein, mouse
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Inflammation Mediators
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Interleukin-1 Receptor-Like 1 Protein
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Interleukin-1beta
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Interleukin-33
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Interleukins
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Membrane Proteins
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Receptors, Interleukin
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Tumor Necrosis Factor-alpha
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Prostaglandin D2