Linked Life Data

9029093

Source:http://linkedlifedata.com/resource/pubmed/id/9029093

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1997-3-5
pubmed:abstractText
Activated lamina propria T cells responding to luminal Ags are thought to be important in celiac disease and Crohn's disease, and T cells responding to foreign MHC products are also important in intestinal graft-vs-host disease and intestinal transplant rejection. However, the mechanism(s) by which T cells mediate damage in the gut is not known. We have previously shown that activation of lamina propria T cells by PWM in explant cultures of second trimester human small intestine produces severe tissue injury, with epithelial cell shedding and loss of villi. In this study, we have investigated the role of matrix metalloproteinases in this system. Organ culture supernatants of explants stimulated with PWM showed a 3-fold increase in the concentration of interstitial collagenase and a 10-fold increase in stromelysin-1 compared with control explant culture supernatants. Tissue inhibitors of metalloproteinase-1 and -2 concentrations were unchanged. Increased metalloproteinase enzymatic activity was detected by gelatin and casein zymography. Western blotting revealed the active forms of interstitial collagenase and stromelysin-1 in PWM-stimulated culture supernatants. Up-regulation of mRNA for interstitial collagenase, stromelysin-1, and gelatinase-B was also seen. Nanomolar amounts of recombinant stromelysin-1 added directly to explants produced rapid severe tissue injury. PWM-induced mucosal injury was inhibited by a synthetic peptidomimetic inhibitor of matrix metalloproteinases. Mesenchymal cells isolated from the mucosa of human fetal small intestine produced increased amounts of interstitial collagenase, gelatinase A, and stromelysin-1 when stimulated with IL-1beta or TNF-alpha. These results suggest that T cell activation in the lamina propria results in increased production of matrix metalloproteinases, which by degrading the lamina propria matrix represent a major pathway by which T cells cause injury in the gut.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
158
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1582-90
pubmed:dateRevised
2010-8-25
pubmed:meshHeading
pubmed-meshheading:9029093-Cell Line, pubmed-meshheading:9029093-Cell-Free System, pubmed-meshheading:9029093-Collagenases, pubmed-meshheading:9029093-Enzyme Activation, pubmed-meshheading:9029093-Enzyme Inhibitors, pubmed-meshheading:9029093-Enzyme Precursors, pubmed-meshheading:9029093-Fetus, pubmed-meshheading:9029093-Gene Expression Regulation, Developmental, pubmed-meshheading:9029093-Glycoproteins, pubmed-meshheading:9029093-Humans, pubmed-meshheading:9029093-Intestinal Mucosa, pubmed-meshheading:9029093-Intestine, Small, pubmed-meshheading:9029093-Metalloendopeptidases, pubmed-meshheading:9029093-Organ Culture Techniques, pubmed-meshheading:9029093-Peptides, pubmed-meshheading:9029093-Recombinant Proteins, pubmed-meshheading:9029093-T-Lymphocytes, pubmed-meshheading:9029093-Tissue Inhibitor of Metalloproteinases
pubmed:year
1997
pubmed:articleTitle
A major role for matrix metalloproteinases in T cell injury in the gut.
pubmed:affiliation
Department of Pediatric Gastroenterology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't