Role of Mitogen-Activated Protein Kinase Pathways in the Production of TNF-alpha, IL-10, and MCP-1 by Mycobacterium tuberculosis H37Rv-Infected Human Blood Monocytes.
- Author:
Chang Hwa SONG
1
;
Ji Sook LEE
;
So Hyun LEE
;
Jae Hyun LIM
;
Kil Soo LEE
;
Saet Byel JUNG
;
Su Young KIM
;
Hwa Jung KIM
;
Jeong Kyu PARK
;
Tae Hyun PAIK
;
Eun Kyeong JO
Author Information
1. Department of Microbiology, College of Medicine, Chungnam National University, 6 Munhwa-dong, Jung-gu, Daejeon, Korea. hayoungj@cnu.ac.kr
- Publication Type:Original Article
- Keywords:
Mycobacterium tuberculosis;
Tumor necrosis factor-a;
Interleukin-10;
Monocyte chemotactic protein-1;
Human blood monocytes;
Mitogen-activated protein kinase pathway
- MeSH:
Chemokine CCL2;
Chemokines;
Cytokines;
Humans*;
Interleukin-10*;
Interleukin-8;
Interleukins;
Macrophages;
MAP Kinase Signaling System;
Monocytes*;
Mycobacterium tuberculosis*;
Mycobacterium*;
Necrosis;
p38 Mitogen-Activated Protein Kinases;
Phosphorylation;
Phosphotransferases;
Protein Kinases*;
Signal Transduction;
Tuberculosis;
Tumor Necrosis Factor-alpha*
- From:Journal of Bacteriology and Virology
2003;33(2):139-150
- CountryRepublic of Korea
- Language:English
-
Abstract:
Clinical manifestations of tuberculosis are closely associated with the initial responses of macrophages to mycobacteria. In this study, we investigated the signal transduction pathways for the secretion of cytokines and chemokines [tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, IL-8, and monocyte chemotactic protein-1 (MCP-1)] in human blood monocytes infected with Mycobacterium tuberculosis H37Rv. M. tuberculosis H37Rv infection induced the secretion of significant amounts of TNF-alpha, IL-10, IL-8, and MCP-1 from human blood monocytes. Analysis of mitogen-activated protein kinase (MAPK) activation [extracellular signal-regulated kinase 1/2 (ERK) and p38 kinase] showed rapid phosphorylation of both subfamilies in response to M. tuberculosis H37Rv. Using highly specific inhibitors of p38 (SB203580) and of MEK-1 (U0126 and PD98059), we found that both p38 and ERK were essential for M. tuberculosis H37Rv-induced TNF-alpha production, whereas activation of the p38 pathway, but not that of ERK, was essential for M. tuberculosis H37Rv-induced IL-10 production. Interestingly, the ERK pathway, but not that of p38, was critical for MCP-1 secretion from human blood monocytes infected with M. tuberculosis H37Rv. However, IL-8 secretion was regulated neither by ERK1/2 nor p38 MAPK. Collectively, these results suggest that induction of the MAPK pathway is required for the expression of TNF-alpha. IL-10, and MCP-1 by human blood monocytes during M. tuberculosis H37Rv infection.
