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Conference Paper: A role for STAT3 in IL-10 downregulation of IFN-γ-induced MHC class II molecule expression on primary human blood macrophages

TitleA role for STAT3 in IL-10 downregulation of IFN-γ-induced MHC class II molecule expression on primary human blood macrophages
Authors
Issue Date2009
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/cytokine
Citation
Tri-Society Annual Conference 2009 of the Society for Leukocyte Biology, International Cytokine Society, & International Society for Interferon and Cytokine Research, Cellular and Cytokine Interactions in Health and Disease, Lisbon, Portugal, 17-21 October, 2009 How to Cite?
AbstractMycobacterium is a successful pathogen in evading immunity. Its recent resurgence is in part due to the spread of AIDS in developing countries. We previously showed that following mycobacterial infection of primary human blood monocytes, PKR is activated leading to the induction of interleukin-10 (IL-10), a potent anti-inflammatory cytokine. IL-10 in turn activates its primary mediator, signal transducer and activator of transcription 3 (STAT3), to exert inhibitory effects on activated immune response. It has been reported that interferon-gamma (IFN-γ) signaling can be suppressed by IL-10, which deactivates macrophages and suppresses cell mediated antigen presentation. During the maturation of major histocompatibility complex class II molecules (MHC-II), cathepsin S, a cysteine protease, plays a significant role in the antigen processing. In light of these, we hypothesize that IL-10-induced and STAT3-mediated signaling pathway interferes with IFN-γ-induced immune responses in primary human blood macrophages. Here, we investigated whether the mycobacteria-induced IL-10 activity perturbs MHC-II antigen levels via its effect on cathepsin S expression in antigen processing. We showed that the expression of both cathepsin S and MHC-II, inducible by IFN-γ, was downregulated in the presence of IL-10. Additionally, we revealed that the inhibitory effect of IL-10 was demonstrated to be independent of the classical IFN-γ-induced JAK/STAT1 signaling cascade or the NF-κB pathway. To delineate the role of STAT3 in mediating the inhibitory effects of IL-10 on MHC-II induction, primary blood macrophages were examined with siRNA technology to silence the transcription factor. Following STAT3 suppression, the expression of IFN-γ-induced surface MHC-II antigens and cathepsin S levels was restored, even in the presence of IL-10. Taken together, our results demonstrated that the immunosuppressive effects of IL-10-STAT3 on MHC-II antigen presentation may occur via the inhibition of cathepsin S expression. These results may provide additional insights into the mechanisms of mycobacterial evasion of immunity.
DescriptionCytokine, 2009, v. 48 n. 1-2, p. 68 abstract no. PP1-100
Poster Presentation I
Persistent Identifierhttp://hdl.handle.net/10722/106287
ISSN
2015 Impact Factor: 2.94
2015 SCImago Journal Rankings: 1.294
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChan, LLYen_HK
dc.contributor.authorCheung, BKWen_HK
dc.contributor.authorLau, ASYen_HK
dc.date.accessioned2010-09-25T23:09:26Z-
dc.date.available2010-09-25T23:09:26Z-
dc.date.issued2009en_HK
dc.identifier.citationTri-Society Annual Conference 2009 of the Society for Leukocyte Biology, International Cytokine Society, & International Society for Interferon and Cytokine Research, Cellular and Cytokine Interactions in Health and Disease, Lisbon, Portugal, 17-21 October, 2009-
dc.identifier.issn1043-4666-
dc.identifier.urihttp://hdl.handle.net/10722/106287-
dc.descriptionCytokine, 2009, v. 48 n. 1-2, p. 68 abstract no. PP1-100-
dc.descriptionPoster Presentation I-
dc.description.abstractMycobacterium is a successful pathogen in evading immunity. Its recent resurgence is in part due to the spread of AIDS in developing countries. We previously showed that following mycobacterial infection of primary human blood monocytes, PKR is activated leading to the induction of interleukin-10 (IL-10), a potent anti-inflammatory cytokine. IL-10 in turn activates its primary mediator, signal transducer and activator of transcription 3 (STAT3), to exert inhibitory effects on activated immune response. It has been reported that interferon-gamma (IFN-γ) signaling can be suppressed by IL-10, which deactivates macrophages and suppresses cell mediated antigen presentation. During the maturation of major histocompatibility complex class II molecules (MHC-II), cathepsin S, a cysteine protease, plays a significant role in the antigen processing. In light of these, we hypothesize that IL-10-induced and STAT3-mediated signaling pathway interferes with IFN-γ-induced immune responses in primary human blood macrophages. Here, we investigated whether the mycobacteria-induced IL-10 activity perturbs MHC-II antigen levels via its effect on cathepsin S expression in antigen processing. We showed that the expression of both cathepsin S and MHC-II, inducible by IFN-γ, was downregulated in the presence of IL-10. Additionally, we revealed that the inhibitory effect of IL-10 was demonstrated to be independent of the classical IFN-γ-induced JAK/STAT1 signaling cascade or the NF-κB pathway. To delineate the role of STAT3 in mediating the inhibitory effects of IL-10 on MHC-II induction, primary blood macrophages were examined with siRNA technology to silence the transcription factor. Following STAT3 suppression, the expression of IFN-γ-induced surface MHC-II antigens and cathepsin S levels was restored, even in the presence of IL-10. Taken together, our results demonstrated that the immunosuppressive effects of IL-10-STAT3 on MHC-II antigen presentation may occur via the inhibition of cathepsin S expression. These results may provide additional insights into the mechanisms of mycobacterial evasion of immunity.-
dc.languageengen_HK
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/cytokine-
dc.relation.ispartofTri-Society Annual Conference of the Society for Leukocyte Biology, International Cytokine Society, & International Society for Interferon and Cytokine Researchen_HK
dc.titleA role for STAT3 in IL-10 downregulation of IFN-γ-induced MHC class II molecule expression on primary human blood macrophagesen_HK
dc.typeConference_Paperen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1043-4666&volume=48&issue=1-2&spage=68 abstract no. PP1&epage=100&date=2009&atitle=A+role+for+STAT3+in+IL-10+downregulation+of+IFN-γ-induced+MHC+class+II+molecule+expression+on+primary+human+blood+macrophages-
dc.identifier.emailChan, LLY: lally@hkucc.hku.hken_HK
dc.identifier.emailCheung, BKW: bkwc@hku.hken_HK
dc.identifier.emailLau, ASY: asylau@hku.hken_HK
dc.identifier.authorityLau, ASY=rp00474en_HK
dc.identifier.doi10.1016/j.cyto.2009.07.223-
dc.identifier.hkuros168390en_HK
dc.identifier.volume48-
dc.identifier.issue1-2-
dc.identifier.spage68-
dc.identifier.epage68-
dc.identifier.isiWOS:000270855100227-

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