TGFbeta1 induces mast cell apoptosis

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Christopher Kepley, Associate Professor (Creator)
The University of North Carolina at Greensboro (UNCG )
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Abstract: Mast cells are potent effectors of the inflammatory response, playing an important role in atopy, bacterial immunity, and animal models of arthritis, multiple sclerosis, and heart disease. Hence controlling mast cell numbers and responsiveness is essential for preventing inflammatory disease. We demonstrate that the cytokine transforming growth factor (TGF) ß1 is a potent inducer of mast cell apoptosis, a finding that was consistent in cultured mouse bone marrow–derived mast cells, peritoneal mast cells, and human mast cells. Cell death appeared to be caused by TGF-mediated repression of interleukin-3 (IL-3) receptor expression and function, leading to mitochondrial damage and activation of an apoptotic cascade acting via p53 and caspases. Although IL-3 receptor expression was reduced within 1 day of TGFß1 stimulation, apoptosis required at least 3 days to occur. This delay in onset is postulated to allow protective mast cell effector functions, protecting the host from infection while preventing the establishment of chronic inflammation. Our data support the theory that TGFß1 is an inhibitor of mast cell survival. The widespread expression of TGFß1 offers this cytokine as an ideal candidate for control of mast cell homeostasis.

Additional Information

Experimental Hematology 2006; 34:579-87
Language: English
Date: 2006
transforming growth factor, mast cells, TGFß1, IL-3

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