Regulatory Role of GSK-3β on NF-κB, Nitric Oxide, and TNF-α in Group A Streptococcal Infection

Abstract EN

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.