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Extracellular-regulated kinase activation regulates replication of Mycobacterium avium intracellularly in primary human monocytes.

Extracellular-regulated kinase activation regulates replication of Mycobacterium avium intracellularly in primary human monocytes. Research Abstract Details 

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  • Extracellular-regulated kinase activation regulates replication of Mycobacterium avium intracellularly in primary human monocytes. Abstract Text:

    Mycobacterium avium-intracellulare (MAI) is a ubiquitous environmental pathogen that causes disseminated infection in immunocompromised patients, such as those with human immunodeficiency virus, interleukin-12 deficiency, or interferon-gamma receptor mutation. Colony morphotypes are associated with MAI pathogenicity. Our previous studies have reported that smooth-transparent (SmT) morphotypes are more virulent and induce less cytokine (interleukin-1beta and tumor necrosis factor-alpha) production by human monocytes than the smooth-domed (SmD) morphotypes. Mitogen-activated protein (MAP) kinases such as extracellular-regulated kinase (ERK) are activated by the phagocytosis of particle antigens in macrophages, and this ERK activation subsequently influences cytokine expression and the control of intracellular pathogen growth. The influence of MAP kinase activation on MAI replication in human monocytes was examined. Peripheral blood monocytes isolated from healthy subjects by Ficoll-Hypaque sedimentation were infected with virulent SmT or avirulent SmD MAI without or with MAP kinase inhibitors. MAP kinase activities were determined by in vitro kinase assay, intracellular MAI growth by CFU assay, and cytokines by enzyme-linked immunosorbent assay. MAI infection induced ERK and p38 activation. Inhibition of ERK by PD98059, but not p38, significantly increased intracellular MAI growth. Tumor necrosis factor-alpha release and interleukin-1beta production in response to MAI were reduced by MAP kinase inhibition. p38 inhibition tended to reduce cytokine production more substantially. These data suggest that ERK activation limits intra-monocytic MAI replication and enhances monocytic cytokine release, whereas p38 activation influences only cytokine release. The effect of MAP kinases on MAI growth might thus be mediated by the modulation of cytokine production.

    Extracellular-regulated kinase activation regulates replication of Mycobacterium avium intracellularly in primary human monocytes. Publishing Authors By Initials

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    Extracellular-regulated kinase activation regulates replication of Mycobacterium avium intracellularly in primary human monocytes. Journal Published:

    PUBLICATION TYPE: Journal Article

    Journal: Cell and tissue research

    VOLUME: 332

    Page Numbers: 237-44

    Journal Abbreviation: Cell Tissue Res.

    ISSN: 0302-766X

    DAY: 12

    MONTH: 03

    YEAR: 2008

    Extracellular-regulated kinase activation regulates replication of Mycobacterium avium intracellularly in primary human monocytes. Information

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    LANGUAGE: eng

    NlmUniqueID: 417625

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    Grant and Affiliation Information for Extracellular-regulated kinase activation regulates replication of Mycobacterium avium intracellularly in primary human monocytes.

    AFFILIATION: Department of Surgery, School of Medicine, Wayne State University, Detroit, MI, USA, hshirats@med.wayne.edu.

    Country: Germany

    Germany Research PublicationGermany Research Publication

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    MEDLINETA: Cell Tissue Res

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