| pubmed-article:15800029 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:15800029 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
| pubmed-article:15800029 | lifeskim:mentions | umls-concept:C0026473 | lld:lifeskim |
| pubmed-article:15800029 | lifeskim:mentions | umls-concept:C0031727 | lld:lifeskim |
| pubmed-article:15800029 | lifeskim:mentions | umls-concept:C0079904 | lld:lifeskim |
| pubmed-article:15800029 | lifeskim:mentions | umls-concept:C0165519 | lld:lifeskim |
| pubmed-article:15800029 | lifeskim:mentions | umls-concept:C1704259 | lld:lifeskim |
| pubmed-article:15800029 | lifeskim:mentions | umls-concept:C1705987 | lld:lifeskim |
| pubmed-article:15800029 | lifeskim:mentions | umls-concept:C0033268 | lld:lifeskim |
| pubmed-article:15800029 | lifeskim:mentions | umls-concept:C1314939 | lld:lifeskim |
| pubmed-article:15800029 | lifeskim:mentions | umls-concept:C1879547 | lld:lifeskim |
| pubmed-article:15800029 | pubmed:issue | 1 | lld:pubmed |
| pubmed-article:15800029 | pubmed:dateCreated | 2005-7-4 | lld:pubmed |
| pubmed-article:15800029 | pubmed:abstractText | Matrix metalloproteinase-9 (MMP-9) is considered to be an important component in the progression of inflammation. Monocytes/macrophages are prominent at inflammation sites, and activation of these cells by stimulants, such as lipopolysaccharide (LPS) or tumor necrosis factor alpha and granulocyte macrophage-colony stimulating factor, leads to the production of significant amounts of MMP-9. Here, we show that LPS stimulation of monocytes results in MMP-9 production through a phosphatidylinositol-3 kinase (PI-3K)/Akt/inhibitor of kappaB (IkappaB) kinase-alpha (IKKalpha)/nuclear factor (NF)-kappaB pathway. This new role for Akt in signaling leading to MMP-9 production was demonstrated by inhibitor and immunoprecipitation studies. LY294002 or wortmannin, inhibitors of PI-3K, suppressed LPS-induced Akt activity and MMP-9 production. Evidence for the participation of Akt in monocyte MMP-9 synthesis was demonstrated by the inhibition of MMP-9 by SH-5, a specific inhibitor of Akt. The mechanism by which Akt regulates MMP-9 is through the activation of NF-kappaB, as shown by coimmunoprecipitation of the phosphorylated form of IKKalpha and Akt as well as the SH-5 suppression of the dissociation of IkappaB from NF-kappaB and the activation of NF-kappaB p65. The role of NF-kappaB in regulation of MMP-9 was demonstrated further by the inhibition of MMP-9 production by proteasome inhibitors, lactacystin and MG-132, which prevented the ubiquitination and dissociation of IkappaB from NF-kappaB. This is the first demonstration that Akt is involved in the signaling pathway leading to the production of monocyte MMP-9 and provides an additional approach in the regulation of this enzyme in human primary monocytes. | lld:pubmed |
| pubmed-article:15800029 | pubmed:language | eng | lld:pubmed |
| pubmed-article:15800029 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15800029 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:15800029 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:15800029 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15800029 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15800029 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:15800029 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:15800029 | pubmed:month | Jul | lld:pubmed |
| pubmed-article:15800029 | pubmed:issn | 0741-5400 | lld:pubmed |
| pubmed-article:15800029 | pubmed:author | pubmed-author:WahlLarry MLM | lld:pubmed |
| pubmed-article:15800029 | pubmed:author | pubmed-author:LuYunbiaoY | lld:pubmed |
| pubmed-article:15800029 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:15800029 | pubmed:volume | 78 | lld:pubmed |
| pubmed-article:15800029 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:15800029 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:15800029 | pubmed:pagination | 259-65 | lld:pubmed |
| pubmed-article:15800029 | pubmed:dateRevised | 2010-11-18 | lld:pubmed |
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| pubmed-article:15800029 | pubmed:year | 2005 | lld:pubmed |
| pubmed-article:15800029 | pubmed:articleTitle | Production of matrix metalloproteinase-9 by activated human monocytes involves a phosphatidylinositol-3 kinase/Akt/IKKalpha/NF-kappaB pathway. | lld:pubmed |
| pubmed-article:15800029 | pubmed:affiliation | Immunopathology Sction, National Institute of Dental and Craniofacial Research, National Institute of Health, Bethesda, MD 20892-4352, USA. | lld:pubmed |
| pubmed-article:15800029 | pubmed:publicationType | Journal Article | lld:pubmed |
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