Involvement of protein tyrosine kinase in Toll-like receptor 4-mediated NF-κB activation in human peripheral blood monocytes

被引:50
作者
Chen, LY
Zuraw, BL
Zhao, M
Liu, FT
Huang, S
Pan, ZXK
机构
[1] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA
[2] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA
[3] La Jolla Inst Allergy & Immunol, San Diego, CA 92121 USA
关键词
inflammation; chemokine; lipopolysaccharide; signal transduction; monocytes;
D O I
10.1152/ajplung.00116.2002
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Bacterial lipopolysaccharide (LPS) is a powerful activator of the innate immune system. Exposure to LPS induces an inflammatory reaction in the lung mediated primarily by human blood monocytes and alveolar macrophages, which release an array of inflammatory chemokines and cytokines including IL-8, TNF-alpha, IL-1beta, and IL-6. The signaling mechanisms utilized by LPS to stimulate the release of cytokines and chemokines are still incompletely understood. Pretreatment with the protein tyrosine kinase-specific inhibitors genistein and herbimycin A effectively blocked LPS-induced NF-kappaB activation as well as IL-8 gene expression in human peripheral blood monocytes. However, when genistein was added 2 min after the addition of LPS, no inhibition was observed. Utilizing a coimmunoprecipitation assay, we further showed that LPS-stimulated tyrosine phosphorylation of Toll-like receptor 4 (TLR4) may be involved in downstream signaling events induced by LPS. These findings provide evidence that LPS-induced NF-kappaB activation and IL-8 gene expression use a signaling pathway requiring protein tyrosine kinase and that such regulation may occur through tyrosine phosphorylation of TLR4.
引用
收藏
页码:L607 / L613
页数:7
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