Mycobacterium tuberculosis 6 kDa early secreted antigenic target stimulates activation of J774 macrophages
- 作者：Singh ; Gyanesh ; Singh ; Balwan ; Trajkovic ; Vladimir ; Sharma ; Pawan
- 关键词：M. tuberculosis ; ESAT-6 ; Macrophages ; Nitric oxide ; IFN-γ
- 刊名：Immunology Letters
- 出版年：2005
- 期刊代码：115_01652478
- 类别：med
- 出版时间：May 15, 2005
- 卷：98
- 期：2
- 页码：180-188
- 文件大小：346 K
摘要
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-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.