Activation of Ca2+-dependent signaling by TLR2

被引:66
作者
Chun, Jarin [1 ]
Prince, Alice [1 ]
机构
[1] Columbia Univ, Coll Phys & Surg, New York, NY 10032 USA
关键词
D O I
10.4049/jimmunol.177.2.1330
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Upon contact with airway epithelial cells, bacterial products activate Ca2+ fluxes that are required for induction of NF-kappa B-dependent gene expression. TLR2 is apically displayed on airway cells, making it a likely transducer linking bacterial stimuli and kinases that affect Ca2+ release. Using biochemical and genetic approaches, we demonstrate that TLR2 ligands stimulate release of Ca2+ from intracellular stores by activating TLR2 phosphorylation by c-Sre, and recruiting PI3K and phospholipase C gamma to affect Ca2+ release through inositol (1,4,5) trisphosphate receptors. In the absence of TLR2, murine macrophages as well as airway cells do not generate Ca2+ fluxes or induce proinflammatory signaling. Thus, Ca2+ participates as a second messenger in TLR2-dependent signaling and provides another target to modulate proinflammatory responses to bacterial infection.
引用
收藏
页码:1330 / 1337
页数:8
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