File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: A role for STAT3 and cathepsin S in IL-10 down-regulation of IFN-γ-induced MHC class II molecule on primary human blood macrophages

TitleA role for STAT3 and cathepsin S in IL-10 down-regulation of IFN-γ-induced MHC class II molecule on primary human blood macrophages
Authors
KeywordsAnti-inflammation
Antigen presentation
Cytokines
Issue Date2010
PublisherFederation of American Societies for Experimental Biology. The Journal's web site is located at http://www.jleukbio.org/
Citation
Journal Of Leukocyte Biology, 2010, v. 88 n. 2, p. 303-311 How to Cite?
AbstractIL-10, a potent anti-inflammatory cytokine, activates its primary mediator STAT3 to exert inhibitory effects on activated immune response. It has been reported that IFN-γ signaling can be suppressed by IL-10, which deactivates macrophages and suppresses cell-mediated antigen presentation. Cathepsin S, a cysteine protease, plays a significant role in the antigen processing. We hypothesize that the IL-10-induced and STAT3-mediated signaling pathway interferes with IFN-γ-induced immune responses in primary human blood macrophages. Here, we investigated whether IL-10 perturbs MHC-II levels via its effect on cathepsin S expression in antigen processing. We showed that the expression of 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 JAK2/STAT1 signaling cascade or the NF-κB pathway. Following STAT3 suppression with specific siRNA, 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. © Society for Leukocyte Biology.
Persistent Identifierhttp://hdl.handle.net/10722/127610
ISSN
2015 Impact Factor: 4.165
2015 SCImago Journal Rankings: 2.463
ISI Accession Number ID
Funding AgencyGrant Number
Research Fund for the Control of Infectious DiseasesRFCID 09080512
Research Grants Council of Hong KongHKU 7594/06M
HKU 7685/09M
University of Hong Kong
Edward SK Hotung Pediatrics Education and Research Fund
Funding Information:

This work was supported by grants to A.S.Y.L. from the Research Fund for the Control of Infectious Diseases (RFCID 09080512) and the Research Grants Council of Hong Kong (HKU 7594/06M and HKU 7685/09M). L.L.Y.C. is the recipient of a postgraduate studentship from The University of Hong Kong and from Edward SK Hotung Pediatrics Education and Research Fund. We thank Dr. Davy Lee and Dr. Thomas Leon for their valuable discussion.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorChan, LLYen_HK
dc.contributor.authorCheung, BKWen_HK
dc.contributor.authorLi, JCBen_HK
dc.contributor.authorLau, ASYen_HK
dc.date.accessioned2010-10-31T13:35:30Z-
dc.date.available2010-10-31T13:35:30Z-
dc.date.issued2010en_HK
dc.identifier.citationJournal Of Leukocyte Biology, 2010, v. 88 n. 2, p. 303-311en_HK
dc.identifier.issn0741-5400en_HK
dc.identifier.urihttp://hdl.handle.net/10722/127610-
dc.description.abstractIL-10, a potent anti-inflammatory cytokine, activates its primary mediator STAT3 to exert inhibitory effects on activated immune response. It has been reported that IFN-γ signaling can be suppressed by IL-10, which deactivates macrophages and suppresses cell-mediated antigen presentation. Cathepsin S, a cysteine protease, plays a significant role in the antigen processing. We hypothesize that the IL-10-induced and STAT3-mediated signaling pathway interferes with IFN-γ-induced immune responses in primary human blood macrophages. Here, we investigated whether IL-10 perturbs MHC-II levels via its effect on cathepsin S expression in antigen processing. We showed that the expression of 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 JAK2/STAT1 signaling cascade or the NF-κB pathway. Following STAT3 suppression with specific siRNA, 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. © Society for Leukocyte Biology.en_HK
dc.languageengen_HK
dc.publisherFederation of American Societies for Experimental Biology. The Journal's web site is located at http://www.jleukbio.org/en_HK
dc.relation.ispartofJournal of Leukocyte Biologyen_HK
dc.subjectAnti-inflammationen_HK
dc.subjectAntigen presentationen_HK
dc.subjectCytokinesen_HK
dc.titleA role for STAT3 and cathepsin S in IL-10 down-regulation of IFN-γ-induced MHC class II molecule on primary human blood macrophagesen_HK
dc.typeArticleen_HK
dc.identifier.emailLi, JCB: jamesli@hku.hken_HK
dc.identifier.emailLau, ASY: asylau@hku.hken_HK
dc.identifier.authorityLi, JCB=rp00496en_HK
dc.identifier.authorityLau, ASY=rp00474en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1189/jlb.1009659en_HK
dc.identifier.pmid20356901-
dc.identifier.scopuseid_2-s2.0-77954336090en_HK
dc.identifier.hkuros171711en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77954336090&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume88en_HK
dc.identifier.issue2en_HK
dc.identifier.spage303en_HK
dc.identifier.epage311en_HK
dc.identifier.isiWOS:000285192200010-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectHIV dysregulation of the toll-like receptor system - implications for pathogenesis-
dc.identifier.scopusauthoridChan, LLY=32867597700en_HK
dc.identifier.scopusauthoridCheung, BKW=9634391200en_HK
dc.identifier.scopusauthoridLi, JCB=23103447500en_HK
dc.identifier.scopusauthoridLau, ASY=7202626202en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats