title: Mycobacterium tuberculosis 6 kDa early secreted antigenic target stimulates activation of J774 macrophages.
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.
authors.affiliation: Immunology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Gyanesh
authors.initials: G
authors.lastname: Singh
authors.forename: Balwan
authors.initials: B
authors.lastname: Singh
authors.forename: Vladimir
authors.initials: V
authors.lastname: Trajkovic
authors.forename: Pawan
authors.initials: P
authors.lastname: Sharma
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism*; D018122:B7-1 Antigen / Q000378:metabolism; D001426:Bacterial Proteins; D002460:Cell Line; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011494:Protein Kinases / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D018122:B7-1 Antigen; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D011494:Protein Kinases