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| Articles
by
Wei-Min Chen |
Total Records (
1 ) for
Wei-Min Chen |
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Yong Jun Yang
,
Wei Chen
,
Svetlana O. Carrigan
,
Wei-Min Chen
,
Kristy Roth
,
Taishin Akiyama
,
Jun-ichiro Inoue
,
Jean S. Marshall
,
Jason N. Berman
and
Tong-Jun Lin
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TRAF6 (tumor necrosis factor-associated factor 6) is an essential adaptor downstream from the tumor necrosis factor (TNF) receptor and Toll-like receptor superfamily members. This molecule is critical for dendritic cell maturation and T cell homeostasis. Here we show that TRAF6 is important in high affinity IgE receptor, FcεRI-mediated mast cell activation. In contrast to dendritic cells and T cells, TRAF6-deficient mast cells matured normally and showed normal IgE-dependent degranulation. Importantly, TRAF6-deficient mast cells showed impaired production of cytokine interleukin-6, CCL-9, interleukin-13, and TNF following FcεRI aggregation. Chromatin immunoprecipitation assay showed decreased NF-κB p65 binding to CCL-9 and TNF promoters in TRAF6-deficient mast cells. Antigen and IgE-induced IκB phosphorylation and NF-κB p65 translocation to the nucleus were diminished in TRAF6-deficient mast cells. NF-κB luciferase activity in response to antigen and IgE stimulation was severely impaired in TRAF6-deficient mast cells. In addition, antigen and IgE-induced phosphorylation of mitogen-activated protein kinase p38 and JNK, but not ERK1/2, was significantly reduced in TRAF6-deficient mast cells. These results identified TRAF6 as an important signal transducer in FcεRI-mediated signaling in mast cells. Our findings implicate TRAF6 as a new adaptor/regulator molecule for allergen-mediated inflammation in allergy. |
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