Staphylococcus aureus induces microglial inflammation via a glycogen synthase kinase 3β-regulated pathway

Yi Lin Cheng, Chi Yun Wang, Wei Ching Huang, Cheng Chieh Tsai, Chia Ling Chen, Ching Fen Shen, A. Yu Chi, Chiou Feng Lin

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

A proinflammatory role for glycogen synthase kinase 3β (GSK-3β) 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-α) and nitric oxide (NO) production, at least in part, via a Toll-like receptor 2-regulated pathway. Neutralization of TNF-α largely blocked heat-inactivated S. aureus-induced NO. Heat-inactivated S. aureus activated GSK-3β, and inhibiting GSK-3β reduced TNF-α production as well as inducible NO synthase (iNOS)/NO biosynthesis. While activation of NF-κB was essential for heat-inactivated S. aureus-induced TNF-α and NO, inhibiting GSK-3β blocked heat-inactivated S. aureus-induced NF-κB p65 nuclear translocation. Additionally, inhibiting GSK-3β enhanced heat-inactivated S. aureus-induced interleukin-10 (IL-10) production (IL-10 is an anti-inflammatory cytokine which inhibits TNF-α production). Neutralization of IL-10 reduced TNF-α downregulation caused by GSK-3β inhibition. These results suggest that GSK-3β regulates heat-inactivated S. aureus-induced TNF-α and NO production in microglia mainly by activating NF-κB and probably by inhibiting IL-10.

Original languageEnglish
Pages (from-to)4002-4008
Number of pages7
JournalInfection and Immunity
Volume77
Issue number9
DOIs
Publication statusPublished - 2009 Sep 1

Fingerprint

Glycogen Synthase Kinase 3
Staphylococcus aureus
Hot Temperature
Inflammation
Tumor Necrosis Factor-alpha
Nitric Oxide
Interleukin-10
Toll-Like Receptor 2
Microglia
Nitric Oxide Synthase Type II
Anti-Inflammatory Agents
Down-Regulation
Cytokines

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Cheng, Yi Lin ; Wang, Chi Yun ; Huang, Wei Ching ; Tsai, Cheng Chieh ; Chen, Chia Ling ; Shen, Ching Fen ; Chi, A. Yu ; Lin, Chiou Feng. / Staphylococcus aureus induces microglial inflammation via a glycogen synthase kinase 3β-regulated pathway. In: Infection and Immunity. 2009 ; Vol. 77, No. 9. pp. 4002-4008.
@article{24ad00747e80418889a64c5e5f57a0a6,
title = "Staphylococcus aureus induces microglial inflammation via a glycogen synthase kinase 3β-regulated pathway",
abstract = "A proinflammatory role for glycogen synthase kinase 3β (GSK-3β) 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-α) and nitric oxide (NO) production, at least in part, via a Toll-like receptor 2-regulated pathway. Neutralization of TNF-α largely blocked heat-inactivated S. aureus-induced NO. Heat-inactivated S. aureus activated GSK-3β, and inhibiting GSK-3β reduced TNF-α production as well as inducible NO synthase (iNOS)/NO biosynthesis. While activation of NF-κB was essential for heat-inactivated S. aureus-induced TNF-α and NO, inhibiting GSK-3β blocked heat-inactivated S. aureus-induced NF-κB p65 nuclear translocation. Additionally, inhibiting GSK-3β enhanced heat-inactivated S. aureus-induced interleukin-10 (IL-10) production (IL-10 is an anti-inflammatory cytokine which inhibits TNF-α production). Neutralization of IL-10 reduced TNF-α downregulation caused by GSK-3β inhibition. These results suggest that GSK-3β regulates heat-inactivated S. aureus-induced TNF-α and NO production in microglia mainly by activating NF-κB and probably by inhibiting IL-10.",
author = "Cheng, {Yi Lin} and Wang, {Chi Yun} and Huang, {Wei Ching} and Tsai, {Cheng Chieh} and Chen, {Chia Ling} and Shen, {Ching Fen} and Chi, {A. Yu} and Lin, {Chiou Feng}",
year = "2009",
month = "9",
day = "1",
doi = "10.1128/IAI.00176-09",
language = "English",
volume = "77",
pages = "4002--4008",
journal = "Infection and Immunity",
issn = "0019-9567",
publisher = "American Society for Microbiology",
number = "9",

}

Staphylococcus aureus induces microglial inflammation via a glycogen synthase kinase 3β-regulated pathway. / Cheng, Yi Lin; Wang, Chi Yun; Huang, Wei Ching; Tsai, Cheng Chieh; Chen, Chia Ling; Shen, Ching Fen; Chi, A. Yu; Lin, Chiou Feng.

In: Infection and Immunity, Vol. 77, No. 9, 01.09.2009, p. 4002-4008.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Staphylococcus aureus induces microglial inflammation via a glycogen synthase kinase 3β-regulated pathway

AU - Cheng, Yi Lin

AU - Wang, Chi Yun

AU - Huang, Wei Ching

AU - Tsai, Cheng Chieh

AU - Chen, Chia Ling

AU - Shen, Ching Fen

AU - Chi, A. Yu

AU - Lin, Chiou Feng

PY - 2009/9/1

Y1 - 2009/9/1

N2 - A proinflammatory role for glycogen synthase kinase 3β (GSK-3β) 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-α) and nitric oxide (NO) production, at least in part, via a Toll-like receptor 2-regulated pathway. Neutralization of TNF-α largely blocked heat-inactivated S. aureus-induced NO. Heat-inactivated S. aureus activated GSK-3β, and inhibiting GSK-3β reduced TNF-α production as well as inducible NO synthase (iNOS)/NO biosynthesis. While activation of NF-κB was essential for heat-inactivated S. aureus-induced TNF-α and NO, inhibiting GSK-3β blocked heat-inactivated S. aureus-induced NF-κB p65 nuclear translocation. Additionally, inhibiting GSK-3β enhanced heat-inactivated S. aureus-induced interleukin-10 (IL-10) production (IL-10 is an anti-inflammatory cytokine which inhibits TNF-α production). Neutralization of IL-10 reduced TNF-α downregulation caused by GSK-3β inhibition. These results suggest that GSK-3β regulates heat-inactivated S. aureus-induced TNF-α and NO production in microglia mainly by activating NF-κB and probably by inhibiting IL-10.

AB - A proinflammatory role for glycogen synthase kinase 3β (GSK-3β) 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-α) and nitric oxide (NO) production, at least in part, via a Toll-like receptor 2-regulated pathway. Neutralization of TNF-α largely blocked heat-inactivated S. aureus-induced NO. Heat-inactivated S. aureus activated GSK-3β, and inhibiting GSK-3β reduced TNF-α production as well as inducible NO synthase (iNOS)/NO biosynthesis. While activation of NF-κB was essential for heat-inactivated S. aureus-induced TNF-α and NO, inhibiting GSK-3β blocked heat-inactivated S. aureus-induced NF-κB p65 nuclear translocation. Additionally, inhibiting GSK-3β enhanced heat-inactivated S. aureus-induced interleukin-10 (IL-10) production (IL-10 is an anti-inflammatory cytokine which inhibits TNF-α production). Neutralization of IL-10 reduced TNF-α downregulation caused by GSK-3β inhibition. These results suggest that GSK-3β regulates heat-inactivated S. aureus-induced TNF-α and NO production in microglia mainly by activating NF-κB and probably by inhibiting IL-10.

UR - http://www.scopus.com/inward/record.url?scp=69049102099&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=69049102099&partnerID=8YFLogxK

U2 - 10.1128/IAI.00176-09

DO - 10.1128/IAI.00176-09

M3 - Article

C2 - 19596777

AN - SCOPUS:69049102099

VL - 77

SP - 4002

EP - 4008

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 9

ER -