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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2007-11-20
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pubmed:abstractText |
Selective expression of cyclooxygenase 2 (COX-2) by macrophages could have an important role in the pathobiology of inflammation. We reported a functional synergism between PU.1 and other transcription factors that contributes to COX-2 gene expression in macrophages. PU.1 resides in the nuclear compartment and is activated by phosphorylation to bind to cognate DNA elements containing a 5'-GGAA/T-3' motif, but the involved kinase has not been discovered. We tested the hypothesis that NF-kappaB-inducing kinase (NIK) regulates COX-2 gene expression in macrophages through inducible phosphorylation of PU.1. Our initial experiments showed an in vitro protein-protein binding interaction between myc-NIK and GST-PU.1. Purified myc-NIK had a strong in vitro kinase activity for purified GST-PU.1, and this activity and production of COX-2 protein is blocked by treatment with a nonspecific kinase inhibitor, 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole. We used short interfering RNA to develop a stable NIK knockdown macrophage cell line that had an approximately 50% decrease in COX-2 protein production and decreased generation of PGD(2), and this was correlated with decreased binding of activated PU.1 to the COX-2 promoter in response to treatment with endotoxin. These findings suggest a novel role for NIK in mediating COX-2 gene expression in endotoxin-treated macrophages by a mechanism that involves phosphorylation of PU.1.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
179
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7868-75
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:18025233-Animals,
pubmed-meshheading:18025233-Cell Line,
pubmed-meshheading:18025233-Cells, Cultured,
pubmed-meshheading:18025233-Cyclooxygenase 2,
pubmed-meshheading:18025233-Endotoxins,
pubmed-meshheading:18025233-Gene Expression Regulation,
pubmed-meshheading:18025233-Humans,
pubmed-meshheading:18025233-Lipopolysaccharides,
pubmed-meshheading:18025233-Macrophages,
pubmed-meshheading:18025233-Mice,
pubmed-meshheading:18025233-Phosphorylation,
pubmed-meshheading:18025233-Protein Binding,
pubmed-meshheading:18025233-Protein-Serine-Threonine Kinases,
pubmed-meshheading:18025233-Proto-Oncogene Proteins,
pubmed-meshheading:18025233-Structure-Activity Relationship,
pubmed-meshheading:18025233-Trans-Activators
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pubmed:year |
2007
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pubmed:articleTitle |
NF-kappaB-inducing kinase regulates cyclooxygenase 2 gene expression in macrophages by phosphorylation of PU.1.
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pubmed:affiliation |
Department of Medicine, University of Illinois, Chicago, IL 60612, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, N.I.H., Extramural
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