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rdf:type |
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lifeskim:mentions |
umls-concept:C0007634,
umls-concept:C0028778,
umls-concept:C0044602,
umls-concept:C0126732,
umls-concept:C0243125,
umls-concept:C0251991,
umls-concept:C0332206,
umls-concept:C0699900,
umls-concept:C1334877,
umls-concept:C1879547,
umls-concept:C1999216
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pubmed:issue |
2
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pubmed:dateCreated |
2002-6-5
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pubmed:abstractText |
The mechanism by which lipopolysaccharide (LPS) or phorbol 12-myristate 13-acetate (PMA) induces production of proinflammatory cytokines in murine macrophages, and the role of phosphatidylinositol 3-kinase (PI3-kinase) have not been well investigated. Activation of nuclear factor kappaB (NF-kappaB) is initiated by the phosphorylation of the inhibitory subunit, IkappaB, which targets IkappaB for degradation and leads to the release of active NF-kappaB. In this study we demonstrate that 2-(4-morpholinyl)-8-phenylchromone (LY294002), which inhibits PI3-kinase, specifically inhibited degradation of IkappaBalpha in RAW264.7 cells stimulated with interferon-gamma (IFN-gamma) plus LPS or IFN-gamma plus PMA. To elucidate the importance of this activity in RAW264.7 cells, we examined tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 production in the activated cells. Pretreatment of the cells with LY294002 resulted in the inhibition of TNF-alpha and IL-6 production in RAW264.7 cells stimulated with IFN-gamma plus LPS or IFN-gamma plus PMA. Furthermore, LY294002 inhibited the production of nitric oxide (NO) in RAW264.7 cells stimulated with IFN-gamma plus LPS or IFN-gamma plus PMA. LY294002 also inhibited inducible NO synthase (iNOS) mRNA expression in the activated RAW264.7 cells. In conclusion, the present results suggest that PI3-kinase is involved in the signal transduction pathway responsible for LPS- or PMA-mediated TNF-alpha and IL-6 production, and that LY294002 inhibits NO generation through blocking the degradation of IkappaBalpha in activated RAW264.7 cells.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-(4-morpholinyl)-8-phenyl-4H-1-benz...,
http://linkedlifedata.com/resource/pubmed/chemical/Chromones,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Morpholines,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappaB inhibitor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:issn |
0742-2091
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
121-30
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:12046690-Animals,
pubmed-meshheading:12046690-Base Sequence,
pubmed-meshheading:12046690-Blotting, Western,
pubmed-meshheading:12046690-Cell Line,
pubmed-meshheading:12046690-Chromones,
pubmed-meshheading:12046690-DNA Primers,
pubmed-meshheading:12046690-DNA-Binding Proteins,
pubmed-meshheading:12046690-Hydrolysis,
pubmed-meshheading:12046690-I-kappa B Proteins,
pubmed-meshheading:12046690-Interferon-gamma,
pubmed-meshheading:12046690-Interleukin-6,
pubmed-meshheading:12046690-Lipopolysaccharides,
pubmed-meshheading:12046690-Macrophages,
pubmed-meshheading:12046690-Mice,
pubmed-meshheading:12046690-Morpholines,
pubmed-meshheading:12046690-Nitric Oxide,
pubmed-meshheading:12046690-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:12046690-Tetradecanoylphorbol Acetate,
pubmed-meshheading:12046690-Tumor Necrosis Factor-alpha
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pubmed:year |
2002
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pubmed:articleTitle |
Degradation of IkappaBalpha in activated RAW264.7 cells is blocked by the phosphatidylinositol 3-kinase inhibitor LY294002.
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pubmed:affiliation |
Department of Oriental Pharmacy, Korea Institute of Oriental Pharmacy, College of Pharmacy, Wonkwang University, Chonbuk.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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