Mycobacterium tuberculosis secretory proteins CFP-10, ESAT-6 and the CFP10:ESAT6 complex inhibit lipopolysaccharide-induced NF-kB transactivation by downregulation of reactive oxidative species (ROS) production

Ganguly, Niladri ; Giang, Pham H ; Gupta, Chitra ; Basu, Sandip K. ; Siddiqui, Imran ; Salunke, Dinakar M. ; Sharma, Pawan (2008) Mycobacterium tuberculosis secretory proteins CFP-10, ESAT-6 and the CFP10:ESAT6 complex inhibit lipopolysaccharide-induced NF-kB transactivation by downregulation of reactive oxidative species (ROS) production Immunology and Cell Biology, 86 . pp. 98-106. ISSN 0818-9641

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Official URL: http://www.nature.com/icb/journal/v86/n1/abs/71001...

Related URL: http://dx.doi.org/10.1038/sj.icb.7100117

Abstract

Mycobacterium tuberculosis (Mtb) causes death of 2-3 million people annually and is considered one of the most successful intracellular pathogens to persist inside the host macrophage. Recent studies have implicated the role of RD-1 region of Mtb genome in the mycobacterial pathogenesis. The role of RD-1-encoded secretory proteins of Mtb in modulation of macrophage function has not been investigated in detail. Here we show that RD-1 encoded two major secretory proteins, namely, culture filtrate protein-10kDa (CFP-10) and early secreted antigenic target-6kDa (ESAT-6), and their 1:1 CFP-10:ESAT6 complex inhibit production of reactive oxidative species (ROS) in RAW264.7 cells. These proteins also downregulated the bacterial lipopolysaccharide (LPS)-induced ROS production, which, in turn, downregulated LPS-induced nuclear factor-kB (NF-kB) p65 DNA-binding activity, as well as inhibited the NF-kB-dependent reporter gene (chloramphenicol acetyl transferase) expression in the treated macrophages. Moreover, addition of N-acetyl cysteine, which is a scavenger of ROS, also inhibited LPS-induced reporter gene expression by scavenging the ROS, thereby preventing NF-kB transactivation. These studies indicate that the secretory proteins CFP-10, ESAT-6 and the CFP10:ESAT6 complex of Mtb can inhibit LPS-induced NF-kB-dependent gene expression via downregulation of ROS production.

Item Type:Article
Source:Copyright of this article belongs to Nature Publishing Group.
Keywords:CFP-10; ESAT-6; Lipopolysaccharide; NF-kB; ROS
ID Code:52479
Deposited On:04 Aug 2011 08:05
Last Modified:04 Aug 2011 08:05

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