Singh, Gyanesh (55470623300)Gyanesh (55470623300)SinghSingh, Balwan (7405638271)Balwan (7405638271)SinghTrajkovic, Vladimir (7004516866)Vladimir (7004516866)TrajkovicSharma, Pawan (7403232336)Pawan (7403232336)Sharma2025-07-022025-07-022005https://doi.org/10.1016/j.imlet.2004.11.011https://www.scopus.com/inward/record.uri?eid=2-s2.0-18044389709&doi=10.1016%2fj.imlet.2004.11.011&partnerID=40&md5=d23765878636b7852ce8ad1c5894a0cdhttps://remedy.med.bg.ac.rs/handle/123456789/14383The 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-γ- 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-γ-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-γ-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. © 2004 Elsevier B.V. All rights reserved.ESAT-6IFN-γM. tuberculosisMacrophagesNitric oxide