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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
Authors:Song Chang-Hwa  Lee Ji-Sook  Lee So-Hyun  Lim Kyu  Kim Hwa-Jung  Park Jeong-Kyu  Paik Tae-Hyun  Jo Eun-Kyeong
Affiliation:(1) Department of Microbiology, College of Medicine, Chungnam National University, 6 Munhwa-dong, Jung-ku, Daejeon, 301-747, Korea
Abstract:The role of mitogen-activated protein kinase (MAPK) pathways in the secretion of tumor necrosis factor (TNF)-agr, 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-agr 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-agr, IL-10, and MCP-1 by human monocytes during M. tuberculosis H37Rv infection.
Keywords:Mycobacterium tuberculosis  tumor necrosis factor-  /content/q64gwm27nu3u1455/xxlarge945.gif"   alt="  agr"   align="  BASELINE"   BORDER="  0"  >  interleukin-10  monocyte chemotactic protein-1  human monocytes  mitogen-activated protein kinase pathway
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