TY - JOUR
T1 - Mycobacterium tuberculosis secretory proteins CFP-10, ESAT-6 and the CFP10
T2 - ESAT6 complex inhibit lipopolysaccharide-induced NF-κB transactivation by downregulation of reactive oxidative species (ROS) production
AU - Ganguly, Niladri
AU - Giang, Pham H.
AU - Gupta, Chitra
AU - Basu, Sandip K.
AU - Siddiqui, Imran
AU - Salunke, Dinakar M.
AU - Sharma, Pawan
PY - 2008/1
Y1 - 2008/1
N2 - 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-10 kDa (CFP-10) and early secreted antigenic target-6 kDa (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-κB (NF-κB) p65 DNA-binding activity, as well as inhibited the NF-κB-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-κB transactivation. These studies indicate that the secretory proteins CFP-10, ESAT-6 and the CFP10:ESAT6 complex of Mtb can inhibit LPS-induced NF-κB-dependent gene expression via downregulation of ROS production.
AB - 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-10 kDa (CFP-10) and early secreted antigenic target-6 kDa (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-κB (NF-κB) p65 DNA-binding activity, as well as inhibited the NF-κB-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-κB transactivation. These studies indicate that the secretory proteins CFP-10, ESAT-6 and the CFP10:ESAT6 complex of Mtb can inhibit LPS-induced NF-κB-dependent gene expression via downregulation of ROS production.
KW - CFP-10
KW - ESAT-6
KW - Lipopolysaccharide
KW - NF-κB
KW - ROS
UR - http://www.scopus.com/inward/record.url?scp=37849052202&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=37849052202&partnerID=8YFLogxK
U2 - 10.1038/sj.icb.7100117
DO - 10.1038/sj.icb.7100117
M3 - Article
C2 - 17909563
AN - SCOPUS:37849052202
VL - 86
SP - 98
EP - 106
JO - Immunology and Cell Biology
JF - Immunology and Cell Biology
SN - 0818-9641
IS - 1
ER -