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Conference Paper: Mycobacterial Evasion of Immunity Via Cytokine Dysregulation: A Potential Role for Mitogen-Activated Protein Kinase Phosphatase-1

TitleMycobacterial Evasion of Immunity Via Cytokine Dysregulation: A Potential Role for Mitogen-Activated Protein Kinase Phosphatase-1
Authors
Issue Date2008
PublisherHong Kong Paediatric Society
Citation
The 1st Annual Scientifc Meeting and 2nd Annual General Meeting of Hong Kong Society for Paediatric Immunology and Infectious Diseases, Hong Kong, 17 May 2008. In Hong Kong Journal of Paediatrics (New Series), 2008, v. 13 n. 4, p. 293 How to Cite?
AbstractIntroduction: Mycobacterium tuberculosis (MTB) is a major cause of morbidity and mortality in the world. To combat against this pathogen, immune cells release cytokines including tumour necrosis factor (TNF)-α, which plays a pivotal role in the development of protective granulomas consisting of macrophages and other immune cells to contain the mycobacteria. Our previous results showed that Bacillus Calmette Guerin (BCG), a mycobacterial model used to investigate the immune response against MTB, stimulates the induction of TNF-α via a double-stranded RNA-dependent protein kinase (PKR) and mitogen-activated protein kinase (MAPK) in human blood monocytes. Since MAPK is regulated by MAPK phosphatase-1 (MKP-1) in response to lipopolysaccharide (LPS), the involvement of MKP-1 in BCG-induced MAPK activation and its consequent cytokine expression was examined. Methods: Primary human blood monocytes were treated with BCG and assayed for MKP-1 expression by quantitative RT-PCR and Western analysis. Results: Our results demonstrated that following exposure to BCG, there was an increase in the expression of MKP-1. Additionally, there was a significant abrogation of BCG-induced MKP-1 expression in the presence of the p38 MAPK and ERK1/2 inhibitors. The results suggested that the induction of MKP-1 was regulated by p38 MAPK and ERK1/2 in response to BCG activation. Next, the roles of MKP-1 in BCG-induced MAPK activation and TNF-α expression were elucidated with the use of MKP-1 siRNA for gene-specific knock-down. Surprisingly, when MKP-1 was blocked by MKP-1 siRNA, there was a significant decrease in the levels of phospho-MAPK and TNF-α inducible by BCG, indicating the phosphatase plays a pivotal role in cellular defense against mycobacterial infection. Conclusion: Taken together, MKP-1 plays a critical role in the regulation of TNF induction in response to mycobacterial infection, and its induction may suggest an effective host defense mechanism to combat the pathogen invasion. Conflict of Interest Statements: There is no conflict of interest (supported in part by grants to ASL from RFCID and RGC-CERG).
Persistent Identifierhttp://hdl.handle.net/10722/105803
ISSN
2015 Impact Factor: 0.194
2015 SCImago Journal Rankings: 0.123

 

DC FieldValueLanguage
dc.contributor.authorCheung, BKWen_HK
dc.contributor.authorLau, ASYen_HK
dc.date.accessioned2010-09-25T22:49:20Z-
dc.date.available2010-09-25T22:49:20Z-
dc.date.issued2008en_HK
dc.identifier.citationThe 1st Annual Scientifc Meeting and 2nd Annual General Meeting of Hong Kong Society for Paediatric Immunology and Infectious Diseases, Hong Kong, 17 May 2008. In Hong Kong Journal of Paediatrics (New Series), 2008, v. 13 n. 4, p. 293-
dc.identifier.issn1013-9923-
dc.identifier.urihttp://hdl.handle.net/10722/105803-
dc.description.abstractIntroduction: Mycobacterium tuberculosis (MTB) is a major cause of morbidity and mortality in the world. To combat against this pathogen, immune cells release cytokines including tumour necrosis factor (TNF)-α, which plays a pivotal role in the development of protective granulomas consisting of macrophages and other immune cells to contain the mycobacteria. Our previous results showed that Bacillus Calmette Guerin (BCG), a mycobacterial model used to investigate the immune response against MTB, stimulates the induction of TNF-α via a double-stranded RNA-dependent protein kinase (PKR) and mitogen-activated protein kinase (MAPK) in human blood monocytes. Since MAPK is regulated by MAPK phosphatase-1 (MKP-1) in response to lipopolysaccharide (LPS), the involvement of MKP-1 in BCG-induced MAPK activation and its consequent cytokine expression was examined. Methods: Primary human blood monocytes were treated with BCG and assayed for MKP-1 expression by quantitative RT-PCR and Western analysis. Results: Our results demonstrated that following exposure to BCG, there was an increase in the expression of MKP-1. Additionally, there was a significant abrogation of BCG-induced MKP-1 expression in the presence of the p38 MAPK and ERK1/2 inhibitors. The results suggested that the induction of MKP-1 was regulated by p38 MAPK and ERK1/2 in response to BCG activation. Next, the roles of MKP-1 in BCG-induced MAPK activation and TNF-α expression were elucidated with the use of MKP-1 siRNA for gene-specific knock-down. Surprisingly, when MKP-1 was blocked by MKP-1 siRNA, there was a significant decrease in the levels of phospho-MAPK and TNF-α inducible by BCG, indicating the phosphatase plays a pivotal role in cellular defense against mycobacterial infection. Conclusion: Taken together, MKP-1 plays a critical role in the regulation of TNF induction in response to mycobacterial infection, and its induction may suggest an effective host defense mechanism to combat the pathogen invasion. Conflict of Interest Statements: There is no conflict of interest (supported in part by grants to ASL from RFCID and RGC-CERG).-
dc.languageengen_HK
dc.publisherHong Kong Paediatric Society-
dc.relation.ispartofHong Kong Journal of Paediatrics (New Series)en_HK
dc.titleMycobacterial Evasion of Immunity Via Cytokine Dysregulation: A Potential Role for Mitogen-Activated Protein Kinase Phosphatase-1en_HK
dc.typeConference_Paperen_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.hkuros145414en_HK
dc.identifier.hkuros145901-

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