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• W2116798307 abstract "Abstract GSK3 regulation of inflammation is targeted by mycobacterial for evasion of immunity resulting in IL-10 induction in the host. Mtb dysregulates monocyte/macrophage functions to produce a large amount of the immunosuppressive cytokine IL-10. An important function of IL-10 in promoting Mtb survival is the suppression of antigen presentation of monocytes/macrophages to T cells. This dampens the host immune responses and provides an opportunity for immune evasion. GSK3 has been shown to control the balance between pro- and anti-inflammatory cytokine productions. Here, we investigated whether GSK3 regulates IL-10 expression and mediates a protective role upon live mycobacterial challenge using BCG as a model. Our results showed that BCG increased Akt phosphorylation and inhibited GSK3 activity, resulting in increased IL-10 production. We confirmed further that suppression of GSK3 activities by a specific chemical inhibitor strongly enhanced BCG-induced IL-10 production. We also showed that IL-10 secreted by BCG-infected human PBMo was a major suppressor of subsequent IFN-γ production by PBMC and HLA-DR expression on PBMo in response to BCG. Neutralization of PBMo-secreted IL-10 by anti-IL-10 antibodies restored the IFN-γ production and HLA-DR surface expression. Taken together, GSK3 negatively regulates mycobacteria-induced IL-10 production in human PBMo. The kinase may play a role in restoring IFN-γ secretions and subsequent antigen presentation in response to mycobacterial infection. In conclusion, our results suggest a significant role for GSK3 in guarding against mycobacterial evasion of immunity via IL-10 induction in the host." @default.
• W2116798307 created "2016-06-24" @default.
• W2116798307 creator A5007018550 @default.
• W2116798307 creator A5037921252 @default.
• W2116798307 creator A5048823930 @default.
• W2116798307 creator A5069235653 @default.
• W2116798307 creator A5069829237 @default.
• W2116798307 date "2009-04-28" @default.
• W2116798307 modified "2023-10-14" @default.
• W2116798307 title "A role for glycogen synthase kinase-3 in antagonizing mycobacterial immune evasion by negatively regulating IL-10 induction" @default.
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• W2116798307 doi "https://doi.org/10.1189/jlb.0708442" @default.
• W2116798307 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19401395" @default.
• W2116798307 hasPublicationYear "2009" @default.
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