title: Regulatory role of GSK-3 β on NF- κ B, nitric oxide, and TNF- α in group A streptococcal infection.
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-3 β (GSK-3 β) is known to regulate inflammatory response in infectious diseases. However, the regulation of GSK-3 β in GAS infection is still unknown. The present study investigates the interaction between GSK-3 β , NF- κ B, and possible related inflammatory mediators in vitro and in a mouse model. The results revealed that GAS could activate NF- κ B, followed by an increased expression of inducible nitric oxide synthase (iNOS) and NO production in a murine macrophage cell line. Activation of GSK-3 β occurred after GAS infection, and inhibition of GSK-3 β reduced iNOS expression and NO production. Furthermore, GSK-3 β inhibitors reduced NF- κ B activation and subsequent TNF- α production, which indicates that GSK-3 β acts upstream of NF- κ B in GAS-infected macrophages. Similar to the in vitro findings, administration of GSK-3 β 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-3 β to moderate the inflammatory effect might be an alternative therapeutic strategy against GAS infection.
authors.affiliation: Department of Internal Medicine, National Cheng Kung University Medical College, Tainan 701, Taiwan.
authors.forename: Yu-Tzu
authors.initials: YT
authors.lastname: Chang
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Chen
authors.forename: Chiou-Feng
authors.initials: CF
authors.lastname: Lin
authors.forename: Shiou-Ling
authors.initials: SL
authors.lastname: Lu
authors.forename: Miao-Huei
authors.initials: MH
authors.lastname: Cheng
authors.forename: Chih-Feng
authors.initials: CF
authors.lastname: Kuo
authors.forename: Yee-Shin
authors.initials: YS
authors.lastname: Lin
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D004797:Enzyme-Linked Immunosorbent Assay; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D013290:Streptococcal Infections; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3