Staphylococcus aureus Induces Microglial Inflammation via a Glycogen Synthase Kinase 3β-Regulated Pathway

被引：43
作者：
Cheng, Yi-Lin [1 ]
Wang, Chi-Yun [1 ,2 ]
Huang, Wei-Ching [1 ,2 ,3 ]
Tsai, Cheng-Chieh [1 ,2 ,4 ]
Chen, Chia-Ling [3 ]
Shen, Ching-Fen [1 ,5 ]
Chi, Chia-Yu [1 ,5 ,6 ]
Lin, Chiou-Feng [1 ,2 ,3 ]
机构：
[1] Natl Cheng Kung Univ, Inst Clin Med, Coll Med, Tainan 701, Taiwan
[2] Natl Cheng Kung Univ, Inst Basic Med Sci, Coll Med, Tainan 701, Taiwan
[3] Natl Cheng Kung Univ, Dept Microbiol & Immunol, Coll Med, Tainan 701, Taiwan
[4] Chung Hwa Univ Med Technol, Dept Nursing, Tainan 701, Taiwan
[5] Natl Cheng Kung Univ, Med Coll Hosp, Dept Pediat, Tainan 701, Taiwan
[6] Natl Hlth Res Inst, Div Infect Dis, Tainan 701, Taiwan
来源：
INFECTION AND IMMUNITY | 2009年 / 77卷 / 09期
关键词：
INDUCED BRAIN-ABSCESS; TUMOR-NECROSIS-FACTOR; GALACTOSAMINE-SENSITIZED MICE; KAPPA-B ACTIVATION; ENTEROTOXIN-B; ORGAN INJURY; KINASE-3-BETA INHIBITION; RANTES PRODUCTION; HEPATIC-INJURY; CYTOKINE STORM;
D O I：
10.1128/IAI.00176-09
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
A proinflammatory role for glycogen synthase kinase 3 beta (GSK-3 beta) has been demonstrated. Here, we addressed its roles on heat-inactivated Staphylococcus aureus-induced microglial inflammation. Heat-inactivated S. aureus induced tumor necrosis factor alpha (TNF-alpha) and nitric oxide (NO) production, at least in part, via a Toll-like receptor 2-regulated pathway. Neutralization of TNF-alpha largely blocked heat-inactivated S. aureus-induced NO. Heat-inactivated S. aureus activated GSK-3 beta, and inhibiting GSK-3 beta reduced TNF-alpha production as well as inducible NO synthase (iNOS)/NO biosynthesis. While activation of NF-kappa B was essential for heat-inactivated S. aureus-induced TNF-alpha and NO, inhibiting GSK-3 beta blocked heat-inactivated S. aureus-induced NF-kappa B p65 nuclear translocation. Additionally, inhibiting GSK-3 beta enhanced heat-inactivated S. aureus-induced interleukin-10 (IL-10) production (IL-10 is an anti-inflammatory cytokine which inhibits TNF-alpha production). Neutralization of IL-10 reduced TNF-alpha downregulation caused by GSK-3 beta inhibition. These results suggest that GSK-3 beta regulates heat-inactivated S. aureus-induced TNF-alpha and NO production in microglia mainly by activating NF-kappa B and probably by inhibiting IL-10.
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收藏
页码：4002 / 4008
页数：7
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