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  • Title: Mycobacterium tuberculosis 6 kDa early secreted antigenic target stimulates activation of J774 macrophages.
    Author: Singh G, Singh B, Trajkovic V, Sharma P.
    Journal: Immunol Lett; 2005 May 15; 98(2):180-8. PubMed ID: 15860216.
    Abstract:
    The influence of the 6 kDa early-secreted antigenic target (ESAT-6) of Mycobacterium tuberculosis on macrophage activation was investigated using J774 macrophage cell line. While without effect if applied alone, ESAT-6 in a dose-dependent manner enhanced nitric oxide (NO) release by IFN-gamma-stimulated J774 cells. However, it completely failed to modulate NO production in J774 cells activated with E. coli lipopolysaccharide. The effect of ESAT-6 on NO synthesis in IFN-gamma-activated J774 cells was accompanied by up-regulated expression of inducible NO synthase (iNOS), an enzyme that catalyzes NO formation. ESAT-6-mediated enhancement of macrophage NO release was markedly suppressed by pharmacological agents that selectively inhibit iNOS enzymatic activity or protein tyrosine kinase and mitogen-activated protein kinase activation. Finally, treatment of J774 macrophages with ESAT-6 also enhanced IFN-gamma-induced expression of the surface molecules B7.1, MHC-II, and ICAM-1. Collectively, these data suggest that ESAT-6 might contribute to macrophage activation in tuberculosis.
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