GSK3 Inhibition Reduces Inflammatory Responses of Microglia and Upregulates Il-10 Production
- Author:
Zuhaida Md Zain
;
Sharmili Vidyadaran
;
Masriana Hassan
- Publication Type:Journal Article
- Keywords:
Microglia;
BV-2 cell lines;
IL-10;
GSK-3;
Neuroinflammation
- MeSH:
Microglia
- From:Malaysian Journal of Medicine and Health Sciences
2017;13(1):1-8
- CountryMalaysia
- Language:English
-
Abstract:
Introduction: Neurodegeneration resulting from pathogen invasion or tissue damage has been associated with
activation of microglia, and exacerbated by the release of neurotoxic mediators such as pro-inflammatory cytokines,
chemokines and reactive oxygen species. Activation of microglia stimulated by lipopolysaccharide is mediated in
part by GSK-3 signaling molecule. Induced IL-10 expression via GSK-3 inhibition is noteworthy since IL-10 has been
remarkably shown to suppress inflammation. Objectives: We aimed to inactivate microglia through inhibition of
GSK-3 signaling and to determine its effects on the production of pro- and anti-inflammatory mediators. Methods:
LPS-stimulated BV-2 cells were treated with a GSK-3 inhibitor (LiCl, NP12, SB216763 or CHIR99021). Inhibition
of GSK-3 was determined by the phosphorylation status of GSK-3β. The effects of GSK-3 inhibition on microglial
inflammatory response were investigated by examining various mediators and CD200R marker. Production of nitric
oxide (NO), glutamate and pro- and anti-inflammatory cytokines were measured using flow cytometry, Griess assay,
glutamate assay and Cytometric Bead Array (CBA) respectively. Results: GSK-3β signaling in LPS-stimulated microglia
was blocked by GSK-3 inhibitor through increased phosphorylation at Serine 9 residue. GSK-3 inhibitors had also
led to reducing in microglia activity via increased expression of CD200R. Inhibition of GSK-3 also diminished
inflammatory mediators such as nitric oxide (NO), glutamate, pro-inflammatory cytokines (TNF-α and IL-6) and
chemokine, MCP-1. Reduction of pro-inflammatory mediators by GSK-3 inhibitor was coincided with increased
IL-10 production. Conclusions: Suppression of microglia-mediated inflammatory response was facilitated by GSK-3
inhibition with associated increased in IL-10 production.
- Full text:P020170614561568775181.pdf
