| Burkholderia pseudomallei-induced expression of a negative regulator, sterile-alpha and Armadillo motif-containing protein, in mouse macrophages: a possible mechanism for suppression of the MyD88-independent pathway. | |
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MedLine Citation:
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PMID: 21555400 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Burkholderia pseudomallei, a causative agent of melioidosis, is a Gram-negative facultative intracellular bacterium that can survive and multiply in macrophages. Previously, we demonstrated that B. pseudomallei failed to activate gene expression downstream of the MyD88-independent pathway, particularly the expression of beta interferon (IFN-β) and inducible nitric oxide synthase (iNOS), leading to the inability of macrophages to kill this bacterium. In the present report, we extended our study to show that B. pseudomallei was able to activate sterile-α and Armadillo motif (SARM)-containing protein, a known negative regulator of the MyD88-independent pathway. Both live B. pseudomallei and heat-killed B. pseudomallei were able to upregulate SARM expression in a time-dependent manner in mouse macrophage cell line RAW 264.7. The expression of SARM required bacterial internalization, as it could be inhibited by cytochalasin D. In addition, the intracellular survival of B. pseudomallei was suppressed in SARM-deficient macrophages. Increased expression of IFN-β and iNOS and degradation of IκBα correlated with enhanced macrophage killing capability. These results demonstrated that B. pseudomallei modulated macrophage defense mechanisms by upregulating SARM, thus leading to the suppression of IFN-β and iNOS needed for bacterial elimination. |
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Authors:
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M Pudla; K Limposuwan; P Utaisincharoen |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-05-09 |
Journal Detail:
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Title: Infection and immunity Volume: 79 ISSN: 1098-5522 ISO Abbreviation: Infect. Immun. Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-06-21 Completed Date: 2011-09-02 Revised Date: 2012-01-02 |
Medline Journal Info:
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Nlm Unique ID: 0246127 Medline TA: Infect Immun Country: United States |
Other Details:
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Languages: eng Pagination: 2921-7 Citation Subset: IM |
Affiliation:
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Department of Microbiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand, scput@mahidol.ac.th. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Armadillo Domain Proteins / biosynthesis*, genetics* Burkholderia pseudomallei / metabolism*, pathogenicity* Cell Line Cytochalasin D / pharmacology I-kappa B Proteins / metabolism Immunoblotting Interferon-beta / metabolism Macrophages / metabolism*, microbiology Melioidosis / genetics, metabolism, microbiology Mice Myeloid Differentiation Factor 88 / metabolism* Nitric Oxide Synthase Type II / metabolism Reverse Transcriptase Polymerase Chain Reaction |
| Chemical | |
Reg. No./Substance:
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0/Armadillo Domain Proteins; 0/I-kappa B Proteins; 0/Myeloid Differentiation Factor 88; 139874-52-5/NF-kappaB inhibitor alpha; 22144-77-0/Cytochalasin D; 77238-31-4/Interferon-beta; EC 1.14.13.39/Nitric Oxide Synthase Type II |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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