Source:http://linkedlifedata.com/resource/pubmed/id/17575075
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2007-9-17
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pubmed:abstractText |
Mycobacterium tuberculosis (MTb) kills approximately 2 million people each year. MTb must drive host tissue destruction to disseminate and also to cause pulmonary cavitation. Matrix metalloproteinase-9 (MMP-9, gelatinase B) is implicated in this Tb-related immunopathology. We demonstrate that conditioned media from MTb-infected monocytes (CoMTb), but not direct infection with MTb, up-regulates MMP-9 gene expression and secretion from primary human bronchial epithelial cells (NHBE). MMP-9 secretion was increased 8.7-fold by CoMTb (P < 0.05) as assayed by gelatin zymography. A549 and 16HBE14o epithelial cell MMP secretion was significantly less than primary NHBE secretion. MMP-9 secretion was decreased 53.2% by inhibition of the p38 mitogen-activated protein kinase (MAPK) by SB203580 (P < 0.01) and 48.3% by inhibition of extracellular signal-regulated kinase with PD98059 (P < 0.05). MMP-9 secretion was prostaglandin independent. TNF-alpha was necessary but not sufficient for MMP-9 up-regulation by the monocyte-epithelial cell network. Soluble factors derived from Tb culture synergized with TNF-alpha to increase MMP-9 secretion by NHBE 6-fold (P < 0.01 compared with either stimulus alone). Together, these data reveal a new mechanism by which host- and pathogen-derived factors act together in MTb infection to drive MAPK-dependent MMP-9 secretion from respiratory epithelial cells.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Bacterial Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP...,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1beta,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 9,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1044-1549
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
37
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
431-7
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17575075-Bacterial Proteins,
pubmed-meshheading:17575075-Epithelial Cells,
pubmed-meshheading:17575075-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:17575075-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:17575075-Humans,
pubmed-meshheading:17575075-Interleukin-1beta,
pubmed-meshheading:17575075-Interleukin-6,
pubmed-meshheading:17575075-Matrix Metalloproteinase 9,
pubmed-meshheading:17575075-Monocytes,
pubmed-meshheading:17575075-Mycobacterium tuberculosis,
pubmed-meshheading:17575075-RNA, Messenger,
pubmed-meshheading:17575075-Respiratory Mucosa,
pubmed-meshheading:17575075-Tuberculosis,
pubmed-meshheading:17575075-Tumor Necrosis Factor-alpha,
pubmed-meshheading:17575075-Up-Regulation,
pubmed-meshheading:17575075-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2007
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pubmed:articleTitle |
Synergistic up-regulation of epithelial cell matrix metalloproteinase-9 secretion in tuberculosis.
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pubmed:affiliation |
Department of Infectious Diseases, Imperial College, Hammersmith Hospital, London, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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