Effects of GSK-3 inhibition on LPS-induced neuroinflammation and IL-10 production in microglia

Microglia are resident macrophages of the central nervous system (CNS) that play a role in the immune surveillance system against various pathogenicities. However, excessive inflammation resulting from activation of microglia has been implicated in the neurodegenerative diseases such as mult...

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Main Author:	Md Zain, Zuhaida
Format:	Thesis
Language:	English
Published:	2016
Subjects:	Glycogen Synthase Kinase 3 Microglia
Online Access:	http://psasir.upm.edu.my/id/eprint/66821/1/FPSK%20%28m%29%202016%2073%20%20IR.pdf
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spelling	my-upm-ir.668212019-02-01T03:18:22Z Effects of GSK-3 inhibition on LPS-induced neuroinflammation and IL-10 production in microglia 2016-09 Md Zain, Zuhaida Microglia are resident macrophages of the central nervous system (CNS) that play a role in the immune surveillance system against various pathogenicities. However, excessive inflammation resulting from activation of microglia has been implicated in the neurodegenerative diseases such as multiple sclerosis. The protein kinase, Glycogen Synthase Kinase (GSK) 3, is involved in many cellular functions including microglial activation. Previously, inhibition of GSK-3 has been shown to reduce inflammation due to decreased production of pro-inflammatory cytokines and increased production of IL-10 in LPS-induced endotoxin shock animal model. Thus, this study was performed to elucidate the possible immunoregulatory effects of GSK-3 inhibitors on activated microglia. We hypothesized that inhibition of GSK-3 would reduce the exaggeration of inflammation in LPS-induced microglial activation with associated increased of IL-10 production. The optimal concentration of LPS and incubation period were optimized and determined by measuring the level of nitric oxide (NO) produced by BV-2, microglia cell lines, without compromising their effect on cell viability. The GSK-3 inhibitors, including lithium chloride (LiCl), SB216763, NP12 and CHIR99021 were used to block GSK-3 activities in the BV-2 cells. All GSK-3 inhibitors tested have shown their efficacy in reducing production of proinflammatory molecules, such as NO, glutamate, MCP-1 and cytokines (TNF- α and IL-6). Interestingly, reduction of pro-inflammatory molecules via GSK-3 inhibition was associated with significant increase in IL-10 production. Furthermore, treatment with GSK-3 inhibitor reduced expression of microglial activation markers, CD11b, while increased expressions of microglial inhibitory markers, CD200R, which confirmed the ability of GSK-3 inhibitor in inhibiting microglial activation. These results indicate that GSK-3 inhibitors effectively reduced pro-inflammatory molecules via inhibition of microglial activation. Moreover, these inhibitors could potentially reduce the severity of neuroinflammation by enhancing IL-10 production. Glycogen Synthase Kinase 3 Microglia 2016-09 Thesis http://psasir.upm.edu.my/id/eprint/66821/ http://psasir.upm.edu.my/id/eprint/66821/1/FPSK%20%28m%29%202016%2073%20%20IR.pdf text en public masters Universiti Putra Malaysia Glycogen Synthase Kinase 3 Microglia
institution	Universiti Putra Malaysia
collection	PSAS Institutional Repository
language	English
topic	Glycogen Synthase Kinase 3 Microglia
spellingShingle	Glycogen Synthase Kinase 3 Microglia Md Zain, Zuhaida Effects of GSK-3 inhibition on LPS-induced neuroinflammation and IL-10 production in microglia
description	Microglia are resident macrophages of the central nervous system (CNS) that play a role in the immune surveillance system against various pathogenicities. However, excessive inflammation resulting from activation of microglia has been implicated in the neurodegenerative diseases such as multiple sclerosis. The protein kinase, Glycogen Synthase Kinase (GSK) 3, is involved in many cellular functions including microglial activation. Previously, inhibition of GSK-3 has been shown to reduce inflammation due to decreased production of pro-inflammatory cytokines and increased production of IL-10 in LPS-induced endotoxin shock animal model. Thus, this study was performed to elucidate the possible immunoregulatory effects of GSK-3 inhibitors on activated microglia. We hypothesized that inhibition of GSK-3 would reduce the exaggeration of inflammation in LPS-induced microglial activation with associated increased of IL-10 production. The optimal concentration of LPS and incubation period were optimized and determined by measuring the level of nitric oxide (NO) produced by BV-2, microglia cell lines, without compromising their effect on cell viability. The GSK-3 inhibitors, including lithium chloride (LiCl), SB216763, NP12 and CHIR99021 were used to block GSK-3 activities in the BV-2 cells. All GSK-3 inhibitors tested have shown their efficacy in reducing production of proinflammatory molecules, such as NO, glutamate, MCP-1 and cytokines (TNF- α and IL-6). Interestingly, reduction of pro-inflammatory molecules via GSK-3 inhibition was associated with significant increase in IL-10 production. Furthermore, treatment with GSK-3 inhibitor reduced expression of microglial activation markers, CD11b, while increased expressions of microglial inhibitory markers, CD200R, which confirmed the ability of GSK-3 inhibitor in inhibiting microglial activation. These results indicate that GSK-3 inhibitors effectively reduced pro-inflammatory molecules via inhibition of microglial activation. Moreover, these inhibitors could potentially reduce the severity of neuroinflammation by enhancing IL-10 production.
format	Thesis
qualification_level	Master's degree
author	Md Zain, Zuhaida
author_facet	Md Zain, Zuhaida
author_sort	Md Zain, Zuhaida
title	Effects of GSK-3 inhibition on LPS-induced neuroinflammation and IL-10 production in microglia
title_short	Effects of GSK-3 inhibition on LPS-induced neuroinflammation and IL-10 production in microglia
title_full	Effects of GSK-3 inhibition on LPS-induced neuroinflammation and IL-10 production in microglia
title_fullStr	Effects of GSK-3 inhibition on LPS-induced neuroinflammation and IL-10 production in microglia
title_full_unstemmed	Effects of GSK-3 inhibition on LPS-induced neuroinflammation and IL-10 production in microglia
title_sort	effects of gsk-3 inhibition on lps-induced neuroinflammation and il-10 production in microglia
granting_institution	Universiti Putra Malaysia
publishDate	2016
url	http://psasir.upm.edu.my/id/eprint/66821/1/FPSK%20%28m%29%202016%2073%20%20IR.pdf
_version_	1747812411721646080

Effects of GSK-3 inhibition on LPS-induced neuroinflammation and IL-10 production in microglia

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