| pubmed-article:19380835 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:19380835 | lifeskim:mentions | umls-concept:C0041296 | lld:lifeskim |
| pubmed-article:19380835 | lifeskim:mentions | umls-concept:C0127082 | lld:lifeskim |
| pubmed-article:19380835 | lifeskim:mentions | umls-concept:C1366876 | lld:lifeskim |
| pubmed-article:19380835 | lifeskim:mentions | umls-concept:C1833235 | lld:lifeskim |
| pubmed-article:19380835 | lifeskim:mentions | umls-concept:C2611812 | lld:lifeskim |
| pubmed-article:19380835 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
| pubmed-article:19380835 | pubmed:issue | 9 | lld:pubmed |
| pubmed-article:19380835 | pubmed:dateCreated | 2009-4-21 | lld:pubmed |
| pubmed-article:19380835 | pubmed:abstractText | Mycobacterium tuberculosis (M. tb) must cause lung disease to spread. Matrix metalloproteinases (MMPs) degrade the extracellular matrix and are implicated in tuberculosis-driven tissue destruction. We investigated signaling pathways regulating macrophage MMP-1 and -7 in human pulmonary tuberculosis and examine the hypothesis that the antimycobacterial drug p-aminosalicylic acid acts by inhibiting such pathways. In primary human macrophages, M. tb up-regulates gene expression and secretion of MMP-1 (interstitial collagenase) and MMP-7 (matrilysin). In tuberculosis patients, immunohistochemical analysis of lung biopsies demonstrates that p38 MAPK is phosphorylated in macrophages surrounding granulomas. In vitro, M. tb drives p38 phosphorylation. p38 inhibition suppresses M. tb-dependent MMP-1 secretion by 57.8% and concurrently increases secretion of its specific inhibitor TIMP-1 by 243.7%, demonstrating that p38 activity regulates matrix degradation by macrophages. p38 signals downstream to the cyclooxygenase 2/PGE(2) pathway. p-Aminosalicyclic acid, an agent used to treat drug-resistant tuberculosis, inhibits M. tb-driven MMP-1 but not MMP-7 gene expression and secretion. PAS acts by blocking PGE(2) production without affecting M. tb growth. In summary, p-aminosalicyclic acid decreases MMP-1 activity by inhibiting a p38 MAPK-PG signaling cascade, suggesting that this pathway is a therapeutic target to reduce inflammatory tissue destruction in tuberculosis. | lld:pubmed |
| pubmed-article:19380835 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19380835 | pubmed:language | eng | lld:pubmed |
| pubmed-article:19380835 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19380835 | pubmed:citationSubset | AIM | lld:pubmed |
| pubmed-article:19380835 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19380835 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:19380835 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19380835 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19380835 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19380835 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19380835 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19380835 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:19380835 | pubmed:month | May | lld:pubmed |
| pubmed-article:19380835 | pubmed:issn | 1550-6606 | lld:pubmed |
| pubmed-article:19380835 | pubmed:author | pubmed-author:FriedlandJon... | lld:pubmed |
| pubmed-article:19380835 | pubmed:author | pubmed-author:RandLucindaL | lld:pubmed |
| pubmed-article:19380835 | pubmed:author | pubmed-author:GreenJustin... | lld:pubmed |
| pubmed-article:19380835 | pubmed:author | pubmed-author:ElkingtonPaul... | lld:pubmed |
| pubmed-article:19380835 | pubmed:author | pubmed-author:SaraivaLuísaL | lld:pubmed |
| pubmed-article:19380835 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:19380835 | pubmed:day | 1 | lld:pubmed |
| pubmed-article:19380835 | pubmed:volume | 182 | lld:pubmed |
| pubmed-article:19380835 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:19380835 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:19380835 | pubmed:pagination | 5865-72 | lld:pubmed |
| pubmed-article:19380835 | pubmed:dateRevised | 2009-11-19 | lld:pubmed |
| pubmed-article:19380835 | pubmed:meshHeading | pubmed-meshheading:19380835... | lld:pubmed |
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| pubmed-article:19380835 | pubmed:meshHeading | pubmed-meshheading:19380835... | lld:pubmed |
| pubmed-article:19380835 | pubmed:meshHeading | pubmed-meshheading:19380835... | lld:pubmed |
| pubmed-article:19380835 | pubmed:meshHeading | pubmed-meshheading:19380835... | lld:pubmed |
| pubmed-article:19380835 | pubmed:meshHeading | pubmed-meshheading:19380835... | lld:pubmed |
| pubmed-article:19380835 | pubmed:meshHeading | pubmed-meshheading:19380835... | lld:pubmed |
| pubmed-article:19380835 | pubmed:year | 2009 | lld:pubmed |
| pubmed-article:19380835 | pubmed:articleTitle | Matrix metalloproteinase-1 is regulated in tuberculosis by a p38 MAPK-dependent, p-aminosalicylic acid-sensitive signaling cascade. | lld:pubmed |
| pubmed-article:19380835 | pubmed:affiliation | Department of Infectious Diseases and Immunity, Imperial College London, Hammersmith Campus, London, United Kingdom. | lld:pubmed |
| pubmed-article:19380835 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:19380835 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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