Regulatory role of GSK-3 β on NF-B, nitric oxide, and TNF-α in group A streptococcal infection

Yu-Tzu Chang, Chia Ling Chen, Chiou Feng Lin, Shiou Ling Lu, Miao Huei Cheng, Chih Feng Kuo, Yee-Shin Lin

Research output: Contribution to journalArticle

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Abstract

Group A streptococcus (GAS) imposes a great burden on humans. Efforts to minimize the associated morbidity and mortality represent a critical issue. Glycogen synthase kinase-3β (GSK-3β) is known to regulate inflammatory response in infectious diseases. However, the regulation of GSK-3β in GAS infection is still unknown. The present study investigates the interaction between GSK-3β, NF-B, and possible related inflammatory mediators in vitro and in a mouse model. The results revealed that GAS could activate NF-B, followed by an increased expression of inducible nitric oxide synthase (iNOS) and NO production in a murine macrophage cell line. Activation of GSK-3β occurred after GAS infection, and inhibition of GSK-3β reduced iNOS expression and NO production. Furthermore, GSK-3β inhibitors reduced NF-B activation and subsequent TNF-α production, which indicates that GSK-3β acts upstream of NF-B in GAS-infected macrophages. Similar to the in vitro findings, administration of GSK-3β inhibitor in an air pouch GAS infection mouse model significantly reduced the level of serum TNF-α and improved the survival rate. The inhibition of GSK-3β to moderate the inflammatory effect might be an alternative therapeutic strategy against GAS infection.

Original languageEnglish
Article number720689
JournalMediators of Inflammation
Volume2013
DOIs
Publication statusPublished - 2013 Apr 2

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Glycogen Synthase Kinase 3
Streptococcal Infections
Nitric Oxide
Streptococcus
Nitric Oxide Synthase Type II
Infection
Macrophages
Communicable Diseases
Survival Rate
Air
Morbidity
Cell Line

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cell Biology

Cite this

Chang, Yu-Tzu ; Chen, Chia Ling ; Lin, Chiou Feng ; Lu, Shiou Ling ; Cheng, Miao Huei ; Kuo, Chih Feng ; Lin, Yee-Shin. / Regulatory role of GSK-3 β on NF-B, nitric oxide, and TNF-α in group A streptococcal infection. In: Mediators of Inflammation. 2013 ; Vol. 2013.
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abstract = "Group A streptococcus (GAS) imposes a great burden on humans. Efforts to minimize the associated morbidity and mortality represent a critical issue. Glycogen synthase kinase-3β (GSK-3β) is known to regulate inflammatory response in infectious diseases. However, the regulation of GSK-3β in GAS infection is still unknown. The present study investigates the interaction between GSK-3β, NF-B, and possible related inflammatory mediators in vitro and in a mouse model. The results revealed that GAS could activate NF-B, followed by an increased expression of inducible nitric oxide synthase (iNOS) and NO production in a murine macrophage cell line. Activation of GSK-3β occurred after GAS infection, and inhibition of GSK-3β reduced iNOS expression and NO production. Furthermore, GSK-3β inhibitors reduced NF-B activation and subsequent TNF-α production, which indicates that GSK-3β acts upstream of NF-B in GAS-infected macrophages. Similar to the in vitro findings, administration of GSK-3β inhibitor in an air pouch GAS infection mouse model significantly reduced the level of serum TNF-α and improved the survival rate. The inhibition of GSK-3β to moderate the inflammatory effect might be an alternative therapeutic strategy against GAS infection.",
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Regulatory role of GSK-3 β on NF-B, nitric oxide, and TNF-α in group A streptococcal infection. / Chang, Yu-Tzu; Chen, Chia Ling; Lin, Chiou Feng; Lu, Shiou Ling; Cheng, Miao Huei; Kuo, Chih Feng; Lin, Yee-Shin.

In: Mediators of Inflammation, Vol. 2013, 720689, 02.04.2013.

Research output: Contribution to journalArticle

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