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Article: A role for glycogen synthase kinase-3 in antagonizing mycobacterial immune evasion by negatively regulating IL-10 induction

TitleA role for glycogen synthase kinase-3 in antagonizing mycobacterial immune evasion by negatively regulating IL-10 induction
Authors
Issue Date2009
PublisherFederation of American Societies for Experimental Biology. The Journal's web site is located at http://www.jleukbio.org/
Citation
Journal Of Leukocyte Biology, 2009, v. 86 n. 2, p. 283-291 How to Cite?
AbstractMtb 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. © Society for Leukocyte Biology.
Persistent Identifierhttp://hdl.handle.net/10722/175978
ISSN
2015 Impact Factor: 4.165
2015 SCImago Journal Rankings: 2.463
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChan, MMPen_US
dc.contributor.authorCheung, BKWen_US
dc.contributor.authorLi, JCBen_US
dc.contributor.authorChan, LLYen_US
dc.contributor.authorLau, ASYen_US
dc.date.accessioned2012-11-26T09:03:11Z-
dc.date.available2012-11-26T09:03:11Z-
dc.date.issued2009en_US
dc.identifier.citationJournal Of Leukocyte Biology, 2009, v. 86 n. 2, p. 283-291en_US
dc.identifier.issn0741-5400en_US
dc.identifier.urihttp://hdl.handle.net/10722/175978-
dc.description.abstractMtb 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. © Society for Leukocyte Biology.en_US
dc.languageengen_US
dc.publisherFederation of American Societies for Experimental Biology. The Journal's web site is located at http://www.jleukbio.org/en_US
dc.relation.ispartofJournal of Leukocyte Biologyen_US
dc.subject.meshAntibodies - Pharmacologyen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshDown-Regulation - Immunologyen_US
dc.subject.meshEnzyme Activation - Drug Effects - Immunologyen_US
dc.subject.meshEnzyme Inhibitors - Pharmacologyen_US
dc.subject.meshGlycogen Synthase Kinase 3 - Antagonists & Inhibitors - Metabolism - Physiologyen_US
dc.subject.meshHla-Dr Antigens - Metabolismen_US
dc.subject.meshHumansen_US
dc.subject.meshImmune Tolerance - Immunologyen_US
dc.subject.meshImmunity, Innate - Immunologyen_US
dc.subject.meshInterferon-Gamma - Metabolism - Secretionen_US
dc.subject.meshInterleukin-10 - Antagonists & Inhibitors - Metabolism - Secretionen_US
dc.subject.meshMonocytes - Immunology - Microbiologyen_US
dc.subject.meshMycobacterium - Immunologyen_US
dc.subject.meshMycobacterium Infections - Immunology - Physiopathologyen_US
dc.subject.meshMycobacterium Bovis - Immunologyen_US
dc.subject.meshOncogene Protein V-Akt - Metabolismen_US
dc.subject.meshPhosphorylationen_US
dc.titleA role for glycogen synthase kinase-3 in antagonizing mycobacterial immune evasion by negatively regulating IL-10 inductionen_US
dc.typeArticleen_US
dc.identifier.emailLi, JCB: jamesli@hku.hken_US
dc.identifier.emailLau, ASY: asylau@hku.hken_US
dc.identifier.authorityLi, JCB=rp00496en_US
dc.identifier.authorityLau, ASY=rp00474en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1189/jlb.0708442en_US
dc.identifier.pmid19401395-
dc.identifier.scopuseid_2-s2.0-69449095622en_US
dc.identifier.hkuros159180-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-69449095622&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume86en_US
dc.identifier.issue2en_US
dc.identifier.spage283en_US
dc.identifier.epage291en_US
dc.identifier.isiWOS:000268454900011-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridChan, MMP=14631706500en_US
dc.identifier.scopusauthoridCheung, BKW=9634391200en_US
dc.identifier.scopusauthoridLi, JCB=23103447500en_US
dc.identifier.scopusauthoridChan, LLY=32867597700en_US
dc.identifier.scopusauthoridLau, ASY=7202626202en_US

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