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Conference Paper: Positive role of mitogen-activated protein kinase phosphatase-1 in regulating the anti-mycobacterial immune responses

TitlePositive role of mitogen-activated protein kinase phosphatase-1 in regulating the anti-mycobacterial immune responses
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?
AbstractTuberculosis remains one of the major epidemic threats to human. It is caused by Mycobacterium tuberculosis (Mtb). This pathogen is recognized by monocytes/macrophages resulting in the release of specific cytokines for eliciting immune responses to control the infection. Of these, tumour necrosis factor-alpha (TNF-α) plays a key role in establishing granulomas to restrict Mtb dissemination. We previously showed that using Bacillus Calmette Guerin (BCG) as a model, mycobacteria induce TNF-α through the activation of double-stranded RNA-dependent protein kinase (PKR) and mitogen-activated protein kinases (MAPK). To control overactivation of MAPK following Gram-negative bacteria infection, MAPK phosphatase-1 (MKP-1) has been postulated to exert negative regulation on MAPK activation. Therefore, we hypothesize MKP-1 modulates mycobacterium-stimulated immune responses. To examine whether BCG can induce MKP-1, primary human blood monocytes (PBMo) were infected with BCG and MKP-1 expression was assayed by quantitative RT-PCR and Western blot. Our results showed that BCG induced the expression of MKP-1 in a time-dependent manner. This MKP-1 expression was found to be positively controlled by extracellular signal-regulated kinase-1 and -2 (ERK1/2) and p38 MAPK. To investigate the role of MKP-1 in regulating the BCG-induced responses, the cellular level of MKP-1 protein was knocked down by MKP-1-specific siRNA. Consequently, we demonstrated the level of TNF-α expression induced by BCG in PBMo was reduced, but its induction by lipopolysaccharide was further augmented. Moreover, the phosphorylation levels of BCG-activated ERK1/2 and p38 MAPK were decreased by the MKP-1 knockdown. Taken together, our results indicated that apart from its well-known negative role in regulating LPS-induced responses, MKP-1 acts as a positive regulator in modulating the BCG-induced activation of ERK1/2 and p38 MAPK, and consequently the induced expression of TNF-α. These results provide new insights into the regulation of proinflammatory cytokines in the pathogenesis of mycobacterial infections.
DescriptionCytokine, 2009, v. 48 n. 1-2, p. 61-62 abstract no. PP1-071
Poster Presentation I
Persistent Identifierhttp://hdl.handle.net/10722/106024
ISSN
2015 Impact Factor: 2.94
2015 SCImago Journal Rankings: 1.294
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorCheung, BKWen_HK
dc.contributor.authorYim, HCHen_HK
dc.contributor.authorLau, ASYen_HK
dc.date.accessioned2010-09-25T22:58:26Z-
dc.date.available2010-09-25T22:58:26Z-
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/10722/106024-
dc.descriptionCytokine, 2009, v. 48 n. 1-2, p. 61-62 abstract no. PP1-071-
dc.descriptionPoster Presentation I-
dc.description.abstractTuberculosis remains one of the major epidemic threats to human. It is caused by Mycobacterium tuberculosis (Mtb). This pathogen is recognized by monocytes/macrophages resulting in the release of specific cytokines for eliciting immune responses to control the infection. Of these, tumour necrosis factor-alpha (TNF-α) plays a key role in establishing granulomas to restrict Mtb dissemination. We previously showed that using Bacillus Calmette Guerin (BCG) as a model, mycobacteria induce TNF-α through the activation of double-stranded RNA-dependent protein kinase (PKR) and mitogen-activated protein kinases (MAPK). To control overactivation of MAPK following Gram-negative bacteria infection, MAPK phosphatase-1 (MKP-1) has been postulated to exert negative regulation on MAPK activation. Therefore, we hypothesize MKP-1 modulates mycobacterium-stimulated immune responses. To examine whether BCG can induce MKP-1, primary human blood monocytes (PBMo) were infected with BCG and MKP-1 expression was assayed by quantitative RT-PCR and Western blot. Our results showed that BCG induced the expression of MKP-1 in a time-dependent manner. This MKP-1 expression was found to be positively controlled by extracellular signal-regulated kinase-1 and -2 (ERK1/2) and p38 MAPK. To investigate the role of MKP-1 in regulating the BCG-induced responses, the cellular level of MKP-1 protein was knocked down by MKP-1-specific siRNA. Consequently, we demonstrated the level of TNF-α expression induced by BCG in PBMo was reduced, but its induction by lipopolysaccharide was further augmented. Moreover, the phosphorylation levels of BCG-activated ERK1/2 and p38 MAPK were decreased by the MKP-1 knockdown. Taken together, our results indicated that apart from its well-known negative role in regulating LPS-induced responses, MKP-1 acts as a positive regulator in modulating the BCG-induced activation of ERK1/2 and p38 MAPK, and consequently the induced expression of TNF-α. These results provide new insights into the regulation of proinflammatory cytokines in the pathogenesis of mycobacterial infections.-
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.titlePositive role of mitogen-activated protein kinase phosphatase-1 in regulating the anti-mycobacterial immune responsesen_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=61&epage=62 abstract no. PP1&date=2009&atitle=Positive+role+of+mitogen-activated+protein+kinase+phosphatase-1+in+regulating+the+anti-mycobacterial+immune+responses-
dc.identifier.emailCheung, BKW: bkwc@hku.hken_HK
dc.identifier.emailYim, HCH: chhyim@graduate.hku.hken_HK
dc.identifier.emailLau, ASY: asylau@hku.hken_HK
dc.identifier.authorityLau, ASY=rp00474en_HK
dc.identifier.doi10.1016/j.cyto.2009.07.194-
dc.identifier.hkuros168393en_HK
dc.identifier.volume48-
dc.identifier.issue1-2-
dc.identifier.spage61-
dc.identifier.epage62-
dc.identifier.isiWOS:000270855100200-

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