Regulatory Role of GSK-3β on NF-κB, Nitric Oxide, and TNF-α in Group A Streptococcal Infection
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 infect...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2013/720689 |
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| author | Yu-Tzu Chang Chia-Ling Chen Chiou-Feng Lin Shiou-Ling Lu Miao-Huei Cheng Chih-Feng Kuo Yee-Shin Lin |
| author_facet | Yu-Tzu Chang Chia-Ling Chen Chiou-Feng Lin Shiou-Ling Lu Miao-Huei Cheng Chih-Feng Kuo Yee-Shin Lin |
| author_sort | Yu-Tzu Chang |
| collection | DOAJ |
| description | 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-κB, and possible related inflammatory mediators in vitro and in a mouse model. The results revealed that GAS could activate NF-κB, 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-κB activation and subsequent TNF-α production, which indicates that GSK-3β acts upstream of NF-κB 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. |
| format | Article |
| id | doaj-art-350de5db0b4c4165ba8498cc23b3b4f0 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-350de5db0b4c4165ba8498cc23b3b4f02025-02-03T05:59:22ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/720689720689Regulatory Role of GSK-3β on NF-κB, Nitric Oxide, and TNF-α in Group A Streptococcal InfectionYu-Tzu Chang0Chia-Ling Chen1Chiou-Feng Lin2Shiou-Ling Lu3Miao-Huei Cheng4Chih-Feng Kuo5Yee-Shin Lin6Department of Internal Medicine, National Cheng Kung University Medical College, Tainan 701, TaiwanDepartment of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan 701, TaiwanInstitute of Clinical Medicine, National Cheng Kung University Medical College, Tainan 701, TaiwanInstitute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan 701, TaiwanDepartment of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan 701, TaiwanDepartment of Nursing, I-Shou University, Kaohsiung 840, TaiwanDepartment of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan 701, TaiwanGroup 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-κB, and possible related inflammatory mediators in vitro and in a mouse model. The results revealed that GAS could activate NF-κB, 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-κB activation and subsequent TNF-α production, which indicates that GSK-3β acts upstream of NF-κB 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.http://dx.doi.org/10.1155/2013/720689 |
| spellingShingle | Yu-Tzu Chang Chia-Ling Chen Chiou-Feng Lin Shiou-Ling Lu Miao-Huei Cheng Chih-Feng Kuo Yee-Shin Lin Regulatory Role of GSK-3β on NF-κB, Nitric Oxide, and TNF-α in Group A Streptococcal Infection Mediators of Inflammation |
| title | Regulatory Role of GSK-3β on NF-κB, Nitric Oxide, and TNF-α in Group A Streptococcal Infection |
| title_full | Regulatory Role of GSK-3β on NF-κB, Nitric Oxide, and TNF-α in Group A Streptococcal Infection |
| title_fullStr | Regulatory Role of GSK-3β on NF-κB, Nitric Oxide, and TNF-α in Group A Streptococcal Infection |
| title_full_unstemmed | Regulatory Role of GSK-3β on NF-κB, Nitric Oxide, and TNF-α in Group A Streptococcal Infection |
| title_short | Regulatory Role of GSK-3β on NF-κB, Nitric Oxide, and TNF-α in Group A Streptococcal Infection |
| title_sort | regulatory role of gsk 3β on nf κb nitric oxide and tnf α in group a streptococcal infection |
| url | http://dx.doi.org/10.1155/2013/720689 |
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