期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 289, 期 33, 页码 23075-23085出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M114.591495
关键词
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资金
- National Institutes of Health [NIDA020120, NIGM094740]
- National Natural Science Foundation of China [81370433]
- Fundamental Research Funds for the Central Universities of China [121020]
The control of IL-10 production in Toll-like receptor (TLR) signals remains to be elucidated. Here, we report that beta-arrestin 2 positively regulates TLR-triggered IL-10 production in a p38 mitogen-activated protein kinase (MAPK)-dependent mechanism. In vitro studies with cells including peritoneal macrophages and HEK293/TLR4 cells have demonstrated that beta-arrestin 2 forms complexes with p38 and facilitates p38 activation after lipopolysaccharide (LPS) stimulation. Deficiency of beta-arrestin 2 and inhibition of p38 MAPK activity both ameliorate TLR4-stimulated IL-10 response. Additionally, in vivo experiments show that mice lacking beta-arrestin 2 produce less amount of IL-10, and are more susceptible to LPS-induced septic shock which is further enhanced by blocking IL-10 signal. These results reveal a novel mechanism by which beta-arrestin 2 negatively regulates TLR4-mediated inflammatory reactions.
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