TGF-beta1 attenuates mediator release and de novo Kit expression by human skin mast cells through a Smad-dependent pathway.
TGF-beta1 attenuates mediator release and de novo Kit expression by human skin mast cells through a Smad-dependent pathway.
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DOI：
10.4049/jimmunol.181.10.7263
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发表时间：
2008-11-15
期刊：
影响因子：
--
通讯作者：
Schwartz LB
中科院分区：
文献类型：
--
作者：
Zhao W;Gomez G;Yu SH;Ryan JJ;Schwartz LB
TGF-β has pleiotropic effects on many cell types at different stages of their development, including mast cells. The present study examines the effects of TGF-β on human skin mast cells of the MCTC type. The expression of TGF-β receptors (TGF-R) was verified at the mRNA and protein levels for TGF-RI and TGF-RII, and at the mRNA level for accessory molecules β-glycan and endoglin. TGF-β did not affect mast cell viability after 1 wk at concentrations ≤10 ng/ml, but at 50 ng/ml caused significant cell death. TGF-β inhibited surface and total expression of Kit in a dose-dependent manner, whereas the surface expression of FcεRI, FcγRI, and FcγRII was not affected. TGF-β inhibited degranulation and cytokine production, but not PGD2 production. TGF-β diminished surface Kit expression through a TGF-RI kinase/Smad-dependent pathway by inhibiting new synthesis of Kit protein, which became evident following internalization and degradation of Kit after mast cells were exposed to the Kit ligand, stem cell factor. In contrast, addition of TGF-β had no discernible effect on surface Kit expression when administered 3 days after stem cell factor, by which time surface Kit levels had returned to baseline. Although both transcription and translation are important for de novo expression of Kit, Kit mRNA levels were not affected by TGF-β. Therefore, transcription of a gene other than Kit might be involved in Kit expression. Finally, activation of mast cells increased their susceptibility to TGF-β-mediated apoptosis, a process that might regulate the survival of activated mast cells in vivo.
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影响因子：
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20.3
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