Role of mitogen-activated protein kinase pathways in the production of tumor necrosis factor-alpha, interleukin-10, and monocyte chemotactic protein-1 by Mycobacterium tuberculosis H37Rv-infected human monocytes.
The role of mitogen-activated protein kinase (MAPK) pathways in the secretion of tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, IL-8, and monocyte chemotactic protein-1 (MCP-1) was investigated in human monocytes that were infected with Mycobacterium tuberculosis H37Rv. Analysis of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 kinase showed rapid phosphorylation of both subfamilies in response to M. tuberculosis H37Rv. Using highly specific inhibitors of p38 (SB203580) and of MAPK kinase-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 monocytes that were infected with M. tuberculosis H37Rv. However, IL-8 secretion was not regulated by ERK1/2 or 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 monocytes during M. tuberculosis H37Rv infection.
Song
Chang-Hwa
CH
Department of Microbiology, College of Medicine, Chungnam National University, 6 Munhwa-dong, Jung-ku, Daejeon 301-747, Korea.
Lee
Ji-Sook
JS
Lee
So-Hyun
SH
Lim
Kyu
K
Kim
Hwa-Jung
HJ
Park
Jeong-Kyu
JK
Paik
Tae-Hyun
TH
Jo
Eun-Kyeong
EK
D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D004789:Enzyme Activation / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology*; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D018932:Chemokine CCL2; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D020928:Mitogen-Activated Protein Kinases