Abstract
The role of mitogen-activated protein kinase (MAPK) signaling pathways in the regulation of TNF-α. and NOS2 production by human monocytes infected with Mycobacterium bovis BCG was examined. Inhibition studies showed that ERK1/2 and p38 MAPK activation were necessary for the monocyte response to M. bovis infection. Analysis of MAPK activation showed rapid phosphorylation of ERK1/2 and p38 in response to M. bovis BCG. Phosphorylation was not due to an autocrine effect of TNF-α secretion, since an anti-TNF-α antibody had no significant effect on the levels of p38 phosphorylation. The inhibitor PD98059 significantly reduced M. bovis BCG-induced TNF-α production and almost completely abrogated phosphorylation of ERK1/2; in addition the potent MEK inhibitor U0126 also abrogated phosphorylation. In contrast, studies using inhibitors selective for ERK1/2 and p38 showed that p38 plays an essential role in the induction of NOS2, whereas the role of ERK1/2 was minor. These results suggest that ERK1/2 and p38 kinases differentially regulate the M. bovis BCG-mediated induction of TNF-α and NOS2 in human monocytes.
Original language | English |
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Pages (from-to) | 66-73 |
Number of pages | 8 |
Journal | Journal of Infection |
Volume | 48 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2004 |
Keywords
- BCG
- MAPK
- NOS2
- TNf-α