| pubmed-article:18945810 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:18945810 | lifeskim:mentions | umls-concept:C0017337 | lld:lifeskim |
| pubmed-article:18945810 | lifeskim:mentions | umls-concept:C0034809 | lld:lifeskim |
| pubmed-article:18945810 | lifeskim:mentions | umls-concept:C0752312 | lld:lifeskim |
| pubmed-article:18945810 | lifeskim:mentions | umls-concept:C0679622 | lld:lifeskim |
| pubmed-article:18945810 | lifeskim:mentions | umls-concept:C0205314 | lld:lifeskim |
| pubmed-article:18945810 | lifeskim:mentions | umls-concept:C0441712 | lld:lifeskim |
| pubmed-article:18945810 | pubmed:issue | 1 | lld:pubmed |
| pubmed-article:18945810 | pubmed:dateCreated | 2009-1-5 | lld:pubmed |
| pubmed-article:18945810 | pubmed:abstractText | Glucocorticoids have major antiinflammatory effects. Because COX-2 is the rate-limiting enzyme for proinflammatory prostaglandins, this study investigated the combinatorial inhibitory role of glucocorticoid receptor (GR) in COX-2 gene induction in macrophages and sought to identify the molecular mechanisms for that inhibition. Glucocorticoid-activated GR repressed COX-2 gene induction by lipopolysaccharide (LPS). Activated GR inhibited LPS-induced activator protein 1 activity, which in turn decreased activating transcription factor 2/c-Jun phosphorylation. The inhibition of MAPK-dependent activating transcription factor 2/c-Jun phosphorylation by GR in COX-2 repression was a result of MAPK phosphatase-1 (MKP-1) induction. Although GR did not inhibit LPS-induced p65 phosphorylation or nuclear factor-kappaB DNA binding activity, deletion of the nuclear factor-kappaB binding site in the COX-2 gene suppressed the ability of glucocorticoid to attenuate COX-2 induction. Chromatin immunoprecipitation and transfection assays revealed that a p65 DNA complex involving GR-bound GR-interacting protein 1 (GRIP1) also contributed to COX-2 repression. Additional knockdown and transfection assays identified other inflammatory genes coordinately regulated by MKP-1 and GRIP1. In summary, activated GR was found to antagonize the LPS-dependent induction of the COX-2 gene via a novel combinatorial mechanism involving MKP-1-mediated activator protein 1 inhibition and GR/GRIP1 recruitment to the p65 DNA complex; moreover, this work facilitated the identification of other GR-responding MKP-1/GRIP1-regulated genes. | lld:pubmed |
| pubmed-article:18945810 | pubmed:language | eng | lld:pubmed |
| pubmed-article:18945810 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18945810 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:18945810 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:18945810 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18945810 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18945810 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18945810 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18945810 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18945810 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:18945810 | pubmed:month | Jan | lld:pubmed |
| pubmed-article:18945810 | pubmed:issn | 0888-8809 | lld:pubmed |
| pubmed-article:18945810 | pubmed:author | pubmed-author:KimSang... | lld:pubmed |
| pubmed-article:18945810 | pubmed:author | pubmed-author:ChoIl JeIJ | lld:pubmed |
| pubmed-article:18945810 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:18945810 | pubmed:volume | 23 | lld:pubmed |
| pubmed-article:18945810 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:18945810 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:18945810 | pubmed:pagination | 86-99 | lld:pubmed |
| pubmed-article:18945810 | pubmed:dateRevised | 2009-11-19 | lld:pubmed |
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| pubmed-article:18945810 | pubmed:year | 2009 | lld:pubmed |
| pubmed-article:18945810 | pubmed:articleTitle | A novel mitogen-activated protein kinase phosphatase-1 and glucocorticoid receptor (GR) interacting protein-1-dependent combinatorial mechanism of gene transrepression by GR. | lld:pubmed |
| pubmed-article:18945810 | pubmed:affiliation | Innovative Drug Research Center for Metabolic and Inflammatory Disease, College of Pharmacy, Seoul National University, Sillim-dong, Kwanak-gu, Seoul 151-742, Korea. | lld:pubmed |
| pubmed-article:18945810 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:18945810 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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