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Article: Interleukin-17A differentially modulates BCG induction of cytokine production in human blood macrophages

TitleInterleukin-17A differentially modulates BCG induction of cytokine production in human blood macrophages
Authors
KeywordsHelper T cells
Inflammation
Tuberculosis
Issue Date2011
PublisherFederation of American Societies for Experimental Biology. The Journal's web site is located at http://www.jleukbio.org/
Citation
Journal Of Leukocyte Biology, 2011, v. 90 n. 2, p. 333-341 How to Cite?
AbstractThe pathogenesis of Mtb depends in part on cytokine cross-regulation between macrophages and T cells in host immunity. Th17 cells produce IL-17A to induce granuloma formation and to restrict mycobacterial dissemination. IL-17A also mediates cytokine responses induced by proinflammatory cytokines such as TNF-α. Our previous results showed that BCG induces IL-6, IL-10, and TNF-α via activity of protein kinases, including dsRNA-activated serine/threonine protein kinase and glycogen synthase kinase-3 in primary human monocytes. Therefore, we investigated whether IL-17A, upon its induction by BCG, plays an additional role to aid the production of downstream proinflammatory cytokines in macrophages. Here, we showed that IL-17A enhanced IL-6 mRNA and protein levels inducible by BCG in a time- and dose-dependent manner, whereas it had no effect on IL-10 and TNF-α production. We also demonstrated that IL-17A activated the phosphorylation of ERK1/2 triggered by BCG. With the use of a specific chemical inhibitor of a MAPK/ERK-activating kinase (MEK1/2), we confirmed the correlation between the enhanced ERK1/2 activation and augmented IL-6 production. Additionally, we revealed that IL-17A acts in concert with BCG-induced TNF-α to enhance the level of IL-6 synthesis. Taken together, our results suggest a significant role of IL-17A to serve as a modulator of cytokine expression in innate immune response during mycobacterial infection. © Society for Leukocyte Biology.
Persistent Identifierhttp://hdl.handle.net/10722/135627
ISSN
2015 Impact Factor: 4.165
2015 SCImago Journal Rankings: 2.463
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grants CouncilHKU7685/09M
Research Fund for the Control of Infectious Diseases09080512
09080542
Department of Health and Welfare Bureau (Hong Kong)
The University of Hong Kong
Funding Information:

This work was supported by grants to A.S.Y.L. from the Hong Kong Research Grants Council (HKU7685/09M) and Research Fund for the Control of Infectious Diseases (09080512) and to J.C.B.L. and A.S.Y.L. from Research Fund for the Control of Infectious Diseases (09080542), Department of Health and Welfare Bureau (Hong Kong). J.W.F. is the recipient of a postgraduate studentship from The University of Hong Kong.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorFang, JWen_HK
dc.contributor.authorLi, JCBen_HK
dc.contributor.authorAu, KYen_HK
dc.contributor.authorYim, HCHen_HK
dc.contributor.authorLau, ASYen_HK
dc.date.accessioned2011-07-27T01:37:54Z-
dc.date.available2011-07-27T01:37:54Z-
dc.date.issued2011en_HK
dc.identifier.citationJournal Of Leukocyte Biology, 2011, v. 90 n. 2, p. 333-341en_HK
dc.identifier.issn0741-5400en_HK
dc.identifier.urihttp://hdl.handle.net/10722/135627-
dc.description.abstractThe pathogenesis of Mtb depends in part on cytokine cross-regulation between macrophages and T cells in host immunity. Th17 cells produce IL-17A to induce granuloma formation and to restrict mycobacterial dissemination. IL-17A also mediates cytokine responses induced by proinflammatory cytokines such as TNF-α. Our previous results showed that BCG induces IL-6, IL-10, and TNF-α via activity of protein kinases, including dsRNA-activated serine/threonine protein kinase and glycogen synthase kinase-3 in primary human monocytes. Therefore, we investigated whether IL-17A, upon its induction by BCG, plays an additional role to aid the production of downstream proinflammatory cytokines in macrophages. Here, we showed that IL-17A enhanced IL-6 mRNA and protein levels inducible by BCG in a time- and dose-dependent manner, whereas it had no effect on IL-10 and TNF-α production. We also demonstrated that IL-17A activated the phosphorylation of ERK1/2 triggered by BCG. With the use of a specific chemical inhibitor of a MAPK/ERK-activating kinase (MEK1/2), we confirmed the correlation between the enhanced ERK1/2 activation and augmented IL-6 production. Additionally, we revealed that IL-17A acts in concert with BCG-induced TNF-α to enhance the level of IL-6 synthesis. Taken together, our results suggest a significant role of IL-17A to serve as a modulator of cytokine expression in innate immune response during mycobacterial infection. © Society for Leukocyte Biology.en_HK
dc.languageengen_US
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.subjectHelper T cellsen_HK
dc.subjectInflammationen_HK
dc.subjectTuberculosisen_HK
dc.subject.meshCytokines - biosynthesis-
dc.subject.meshInterleukin-17 - immunology-
dc.subject.meshMacrophages - metabolism - virology-
dc.subject.meshMycobacterium bovis - immunology-
dc.subject.meshTranscriptional Activation - immunology-
dc.titleInterleukin-17A differentially modulates BCG induction of cytokine production in human blood macrophagesen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0741-5400&volume=90&issue=2&spage=333&epage=341&date=2011&atitle=Interleukin-17A+differentially+modulates+BCG+induction+of+cytokine+production+in+human+blood+macrophages-
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_subscribed_fulltext-
dc.identifier.doi10.1189/jlb.0510311en_HK
dc.identifier.pmid21521755-
dc.identifier.scopuseid_2-s2.0-79961079873en_HK
dc.identifier.hkuros186616en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79961079873&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume90en_HK
dc.identifier.issue2en_HK
dc.identifier.spage333en_HK
dc.identifier.epage341en_HK
dc.identifier.eissn1938-3673-
dc.identifier.isiWOS:000293338500013-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectEnhancement of innate immunity to the pathogen infection: anti-mycobacterial effect of IL-17-
dc.relation.projectFactors affecting mycobacteria evasion of immunity: effects of HIV on cellular signaling and kinases-
dc.identifier.scopusauthoridFang, JW=36150695100en_HK
dc.identifier.scopusauthoridLi, JCB=23103447500en_HK
dc.identifier.scopusauthoridAu, KY=36774379800en_HK
dc.identifier.scopusauthoridYim, HCH=15752404600en_HK
dc.identifier.scopusauthoridLau, ASY=7202626202en_HK

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