TGF-ß1 Suppresses IL-33-Induced Mast Cell Function.
J Immunol
; 199(3): 866-873, 2017 08 01.
Article
in En
| MEDLINE
| ID: mdl-28637902
ABSTRACT
TGF-ß1 is involved in many pathological conditions, including autoimmune disorders, cancer, and cardiovascular and allergic diseases. We have previously found that TGF-ß1 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-ß on IL-33-mediated mast cell activation. Bone marrow-derived mast cells cultured in TGF-ß1, ß2, or ß3 showed reduced IL-33-mediated production of TNF, IL-6, IL-13, and MCP-1 in a concentration-dependent manner. TGF-ß1 inhibited IL-33-mediated Akt and ERK phosphorylation as well as NF-κB- and AP-1-mediated transcription. These effects were functionally important, as TGF-ß1 injection suppressed IL-33-induced systemic cytokines in vivo and inhibited IL-33-mediated cytokine release from human mast cells. TGF-ß1 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-ß1 on IgE-mediated activation, demonstrate that TGF-ß1 can provide broad inhibitory signals to activated mast cells.
Full text:
1
Database:
MEDLINE
Main subject:
Transforming Growth Factor beta1
/
Interleukin-33
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Mast Cells
Limits:
Animals
/
Humans
Language:
En
Journal:
J Immunol
Year:
2017
Type:
Article