GSK3 inhibition reduces inflammatory responses of microglia and upregulates Il-10 production
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...
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| Format: | Article |
| Language: | English |
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Faculty of Medicine and Health Sciences, Universiti Putra Malaysia
2017
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| Online Access: | http://psasir.upm.edu.my/id/eprint/52556/1/2017050314414101_MJMHS_Jan_2017_-_0024_GSK_3_.pdf |
| _version_ | 1796975774730813440 |
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| author | Md Zain, Zuhaida Vidyadaran, Sharmili Hassan, Masriana |
| author_facet | Md Zain, Zuhaida Vidyadaran, Sharmili Hassan, Masriana |
| author_sort | Md Zain, Zuhaida |
| collection | UPM |
| description | 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. |
| first_indexed | 2024-03-06T09:16:17Z |
| format | Article |
| id | upm.eprints-52556 |
| institution | Universiti Putra Malaysia |
| language | English |
| last_indexed | 2024-03-06T09:16:17Z |
| publishDate | 2017 |
| publisher | Faculty of Medicine and Health Sciences, Universiti Putra Malaysia |
| record_format | dspace |
| spelling | upm.eprints-525562017-06-07T02:50:36Z http://psasir.upm.edu.my/id/eprint/52556/ GSK3 inhibition reduces inflammatory responses of microglia and upregulates Il-10 production Md Zain, Zuhaida Vidyadaran, Sharmili Hassan, Masriana 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. Faculty of Medicine and Health Sciences, Universiti Putra Malaysia 2017 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/52556/1/2017050314414101_MJMHS_Jan_2017_-_0024_GSK_3_.pdf Md Zain, Zuhaida and Vidyadaran, Sharmili and Hassan, Masriana (2017) GSK3 inhibition reduces inflammatory responses of microglia and upregulates Il-10 production. Malaysian Journal of Medicine and Health Sciences, 13 (1). pp. 1-8. ISSN 1675-8544 http://www.medic.upm.edu.my/upload/dokumen/2017050314414101_MJMHS_Jan_2017_-_0024_GSK_3_.pdf |
| spellingShingle | Md Zain, Zuhaida Vidyadaran, Sharmili Hassan, Masriana GSK3 inhibition reduces inflammatory responses of microglia and upregulates Il-10 production |
| title | GSK3 inhibition reduces inflammatory responses of microglia and upregulates Il-10 production |
| title_full | GSK3 inhibition reduces inflammatory responses of microglia and upregulates Il-10 production |
| title_fullStr | GSK3 inhibition reduces inflammatory responses of microglia and upregulates Il-10 production |
| title_full_unstemmed | GSK3 inhibition reduces inflammatory responses of microglia and upregulates Il-10 production |
| title_short | GSK3 inhibition reduces inflammatory responses of microglia and upregulates Il-10 production |
| title_sort | gsk3 inhibition reduces inflammatory responses of microglia and upregulates il 10 production |
| url | http://psasir.upm.edu.my/id/eprint/52556/1/2017050314414101_MJMHS_Jan_2017_-_0024_GSK_3_.pdf |
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