TGF-?1 Suppresses IL-33-Induced Mast Cell Function.

ABSTRACT: TGF-?1 is involved in many pathological conditions, including autoimmune disorders, cancer, and cardiovascular and allergic diseases. We have previously found that TGF-?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-? on IL-33-mediated mast cell activation. Bone marrow-derived mast cells cultured in TGF-?1, ?2, or ?3 showed reduced IL-33-mediated production of TNF, IL-6, IL-13, and MCP-1 in a concentration-dependent manner. TGF-?1 inhibited IL-33-mediated Akt and ERK phosphorylation as well as NF-?B- and AP-1-mediated transcription. These effects were functionally important, as TGF-?1 injection suppressed IL-33-induced systemic cytokines in vivo and inhibited IL-33-mediated cytokine release from human mast cells. TGF-?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-?1 on IgE-mediated activation, demonstrate that TGF-?1 can provide broad inhibitory signals to activated mast cells.

SUBMITTER: Ndaw VS 

PROVIDER: S-EPMC5538185 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature