Interleukin (IL)-33 induces the release of pro-inflammatory mediators by mast cells.
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.
Moulin
David
D
Division of Rheumatology, University Hospital, University of Geneva School of Medicine, 26 Avenue Beau-Séjour, 1211, Geneva 14, Switzerland.
Donzé
Olivier
O
Talabot-Ayer
Dominique
D
Mézin
Françoise
F
Palmer
Gaby
G
Gabay
Cem
C
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000276:immunology* / Q000378:metabolism; D000072179:Interleukin-1 Receptor-Like 1 Protein; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000276:immunology; D000067596:Interleukin-33; D007378:Interleukins / Q000276:immunology / Q000494:pharmacology*; D008407:Mast Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D015230:Prostaglandin D2 / Q000096:biosynthesis / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D018123:Receptors, Interleukin; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D018836:Inflammation Mediators; D000072179:Interleukin-1 Receptor-Like 1 Protein; D053583:Interleukin-1beta; D000067596:Interleukin-33; D007378:Interleukins; D008565:Membrane Proteins; D018123:Receptors, Interleukin; D014409:Tumor Necrosis Factor-alpha; D015230:Prostaglandin D2