Interleukin (IL)-33 induces the release of pro-inflammatory mediators by mast cells

David Moulin (1) , Olivier Donzé , Dominique Talabot-Ayer (1) , Françoise Mezin (1) , Gaby Palmer (1) , Cem Gabay (1)

1 UNIGE - Université de Genève = University of Geneva

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-1b, TNF-a, MCP-1, and PGD2 production in BMMC. By RNase protection assay, we demonstrated that IL-33 increased IL-6 and IL-1b 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 inflamma-tory diseases by targeting IL-33.

Mots clés: Cytokine; Mast cells; Inflammation

Domaines: Rhumatologie et système ostéo-articulaire; Biochimie, Biologie Moléculaire

David Moulin, Olivier Donzé, Dominique Talabot-Ayer, Françoise Mezin, Gaby Palmer, et al.. Interleukin (IL)-33 induces the release of pro-inflammatory mediators by mast cells. Cytokine, 2007, 40 (3), pp.216-225. ⟨10.1016/j.cyto.2007.09.013⟩. ⟨hal-01715320⟩