TGF-β1 Suppresses IL-33-Induced Mast Cell Function

TGF-beta 1 is involved in many pathological conditions, including autoimmune disorders, cancer, and cardiovascular and allergic diseases. We have previously found that TGF-beta 1 can suppress IgE-mediated mast cell activation of human and mouse mast cells. IL-33 is a member of the IL-1 family capable of inducing mast cell responses and enhancing IgE-mediated activation. In this study, we investigated the effects of TGF-beta on IL-33-mediated mast cell activation. Bone marrow-derived mast cells cultured in TGF-beta 1, beta 2, or beta 3 showed reduced IL-33-mediated production of TNF, IL-6, IL-13, and MCP-1 in a concentration-dependent manner. TGF-beta 1 inhibited IL-33-mediated Akt and ERK phosphorylation as well as NF-kappa B- and AP-1-mediated transcription. These effects were functionally important, as TGF-beta 1 injection suppressed IL-33-induced systemic cytokines in vivo and inhibited IL-33-mediated cytokine release from human mast cells. TGF-beta 1 also suppressed the combined effects of IL-33 and IgE-mediated activation on mouse and human mast cells. The role of IL-33 in the pathogenesis of allergic diseases is incompletely understood. These findings, consistent with our previously reported effects of TGF-beta 1 on IgE-mediated activation, demonstrate that TGF-beta 1 can provide broad inhibitory signals to activated mast cells.