Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-9-17
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1044-1549
pubmed:author
pubmed:issnType
Print
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
431-7
pubmed:dateRevised
2009-11-19
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
pubmed:year
2007
pubmed:articleTitle
Synergistic up-regulation of epithelial cell matrix metalloproteinase-9 secretion in tuberculosis.
pubmed:affiliation
Department of Infectious Diseases, Imperial College, Hammersmith Hospital, London, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't