Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2008-10-8
pubmed:abstractText
Macrophages have the capacity to proliferate in response to specific growth factors, such as macrophage-colony stimulating factor (M-CSF). In the presence of several cytokines and activating factors, macrophages undergo growth arrest, become activated, and participate in the development of an immune response. We have previously observed that activation of extracellularly regulated kinase 1/2 (ERK-1/2) is required for macrophage proliferation in response to growth factors. A short and early pattern of ERK activity correlated with the proliferative response. In contrast, slightly prolonged patterns of activity of these kinases were induced by signals that lead to macrophage activation and growth arrest. IFN-gamma is the main endogenous Th1-type macrophage activator. Here we report that stimulation with IFN-gamma prolongs the pattern of ERK activity induced by M-CSF in macrophages. These effects correlate with IFN-gamma-mediated inhibition of the expression of several members of the MAPK phosphatase family, namely MKP-1, -2, and -4. Moreover, inhibition of MKP-1 expression using siRNA technology or synthetic inhibitors also led to elongated ERK activity and significant blockage of M-CSF-dependent proliferation. These data suggest that subtle changes in the time course of activity of members of the MAPK family contribute to the antiproliferative effects of IFN-gamma in macrophages.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1528-0020
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
112
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3274-82
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
IFN-{gamma}-mediated inhibition of MAPK phosphatase expression results in prolonged MAPK activity in response to M-CSF and inhibition of proliferation.
pubmed:affiliation
Nuclear Receptor Group, Department of Physiology, School of Biology, University of Barcelona, Barcelona, Spain.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't