File Download
There are no files associated with this item.
Links for fulltext
(May Require Subscription)
- Publisher Website: 10.1189/jlb.0708442
- Scopus: eid_2-s2.0-69449095622
- PMID: 19401395
- WOS: WOS:000268454900011
- Find via
Supplementary
- Citations:
- Appears in Collections:
Article: A role for glycogen synthase kinase-3 in antagonizing mycobacterial immune evasion by negatively regulating IL-10 induction
Title | A role for glycogen synthase kinase-3 in antagonizing mycobacterial immune evasion by negatively regulating IL-10 induction |
---|---|
Authors | |
Keywords | Cytokines Human Monocytes/macrophages Mycobacteria Signal transduction |
Issue Date | 2009 |
Publisher | Federation 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? |
Abstract | 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. © Society for Leukocyte Biology. |
Persistent Identifier | http://hdl.handle.net/10722/175978 |
ISSN | 2023 Impact Factor: 3.6 2023 SCImago Journal Rankings: 1.521 |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Chan, MMP | en_US |
dc.contributor.author | Cheung, BKW | en_US |
dc.contributor.author | Li, JCB | en_US |
dc.contributor.author | Chan, LLY | en_US |
dc.contributor.author | Lau, ASY | en_US |
dc.date.accessioned | 2012-11-26T09:03:11Z | - |
dc.date.available | 2012-11-26T09:03:11Z | - |
dc.date.issued | 2009 | en_US |
dc.identifier.citation | Journal Of Leukocyte Biology, 2009, v. 86 n. 2, p. 283-291 | en_US |
dc.identifier.issn | 0741-5400 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/175978 | - |
dc.description.abstract | 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. © Society for Leukocyte Biology. | en_US |
dc.language | eng | en_US |
dc.publisher | Federation of American Societies for Experimental Biology. The Journal's web site is located at http://www.jleukbio.org/ | en_US |
dc.relation.ispartof | Journal of Leukocyte Biology | en_US |
dc.subject | Cytokines | - |
dc.subject | Human | - |
dc.subject | Monocytes/macrophages | - |
dc.subject | Mycobacteria | - |
dc.subject | Signal transduction | - |
dc.subject.mesh | Antibodies - Pharmacology | en_US |
dc.subject.mesh | Cells, Cultured | en_US |
dc.subject.mesh | Down-Regulation - Immunology | en_US |
dc.subject.mesh | Enzyme Activation - Drug Effects - Immunology | en_US |
dc.subject.mesh | Enzyme Inhibitors - Pharmacology | en_US |
dc.subject.mesh | Glycogen Synthase Kinase 3 - Antagonists & Inhibitors - Metabolism - Physiology | en_US |
dc.subject.mesh | Hla-Dr Antigens - Metabolism | en_US |
dc.subject.mesh | Humans | en_US |
dc.subject.mesh | Immune Tolerance - Immunology | en_US |
dc.subject.mesh | Immunity, Innate - Immunology | en_US |
dc.subject.mesh | Interferon-Gamma - Metabolism - Secretion | en_US |
dc.subject.mesh | Interleukin-10 - Antagonists & Inhibitors - Metabolism - Secretion | en_US |
dc.subject.mesh | Monocytes - Immunology - Microbiology | en_US |
dc.subject.mesh | Mycobacterium - Immunology | en_US |
dc.subject.mesh | Mycobacterium Infections - Immunology - Physiopathology | en_US |
dc.subject.mesh | Mycobacterium Bovis - Immunology | en_US |
dc.subject.mesh | Oncogene Protein V-Akt - Metabolism | en_US |
dc.subject.mesh | Phosphorylation | en_US |
dc.title | A role for glycogen synthase kinase-3 in antagonizing mycobacterial immune evasion by negatively regulating IL-10 induction | en_US |
dc.type | Article | en_US |
dc.identifier.email | Li, JCB: jamesli@hku.hk | en_US |
dc.identifier.email | Lau, ASY: asylau@hku.hk | en_US |
dc.identifier.authority | Li, JCB=rp00496 | en_US |
dc.identifier.authority | Lau, ASY=rp00474 | en_US |
dc.description.nature | link_to_subscribed_fulltext | en_US |
dc.identifier.doi | 10.1189/jlb.0708442 | en_US |
dc.identifier.pmid | 19401395 | - |
dc.identifier.scopus | eid_2-s2.0-69449095622 | en_US |
dc.identifier.hkuros | 159180 | - |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-69449095622&selection=ref&src=s&origin=recordpage | en_US |
dc.identifier.volume | 86 | en_US |
dc.identifier.issue | 2 | en_US |
dc.identifier.spage | 283 | en_US |
dc.identifier.epage | 291 | en_US |
dc.identifier.isi | WOS:000268454900011 | - |
dc.publisher.place | United States | en_US |
dc.identifier.scopusauthorid | Chan, MMP=14631706500 | en_US |
dc.identifier.scopusauthorid | Cheung, BKW=9634391200 | en_US |
dc.identifier.scopusauthorid | Li, JCB=23103447500 | en_US |
dc.identifier.scopusauthorid | Chan, LLY=32867597700 | en_US |
dc.identifier.scopusauthorid | Lau, ASY=7202626202 | en_US |
dc.identifier.issnl | 0741-5400 | - |