Differential induction of TNF-α and NOS2 by mitogen-activated protein kinase signaling pathways during Mycobacterium bovis infection

P. Méndez-Samperio, H. Ayala, A. Trejo, F. A. Ramírez

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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. © 2003 The British Infection Society. Published by Elsevier Ltd. All rights reserved.
Original languageAmerican English
Pages (from-to)66-73
Number of pages58
JournalJournal of Infection
DOIs
StatePublished - 1 Jan 2004

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phosphorylation
Mycobacterium Infections
Phosphorylation
infectious diseases
Mycobacterium bovis
Mitogen-Activated Protein Kinases
monocytes
induction
proteins
Proteins
inhibitors
Chemical activation
Monocytes
activation
secretions
Mitogen-Activated Protein Kinase Kinases
p38 Mitogen-Activated Protein Kinases
antibodies
Antibodies
Phosphotransferases

Cite this

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title = "Differential induction of TNF-α and NOS2 by mitogen-activated protein kinase signaling pathways during Mycobacterium bovis infection",
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. {\circledC} 2003 The British Infection Society. Published by Elsevier Ltd. All rights reserved.",
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Differential induction of TNF-α and NOS2 by mitogen-activated protein kinase signaling pathways during Mycobacterium bovis infection. / Méndez-Samperio, P.; Ayala, H.; Trejo, A.; Ramírez, F. A.

In: Journal of Infection, 01.01.2004, p. 66-73.

Research output: Contribution to journalArticleResearchpeer-review

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AB - 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. © 2003 The British Infection Society. Published by Elsevier Ltd. All rights reserved.

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