Regulatory role of GSK-3 ? on NF- ? B, nitric oxide, and TNF- ? 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 ? (GSK-3 ?) is known to regulate inflammatory response in infectious diseases. However, the regulation of GSK-3 ? in GAS infection is still unknown. The present study investigates the interaction between GSK-3 ? , 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-3 ? occurred after GAS infection, and inhibition of GSK-3 ? reduced iNOS expression and NO production. Furthermore, GSK-3 ? inhibitors reduced NF- ? B activation and subsequent TNF- ? production, which indicates that GSK-3 ? acts upstream of NF- ? B in GAS-infected macrophages. Similar to the in vitro findings, administration of GSK-3 ? inhibitor in an air pouch GAS infection mouse model significantly reduced the level of serum TNF- ? and improved the survival rate. The inhibition of GSK-3 ? to moderate the inflammatory effect might be an alternative therapeutic strategy against GAS infection.

SUBMITTER: Chang YT 

PROVIDER: S-EPMC3603300 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature