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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0026809,
umls-concept:C0027950,
umls-concept:C0162638,
umls-concept:C0185117,
umls-concept:C0205349,
umls-concept:C0291573,
umls-concept:C0333348,
umls-concept:C0441655,
umls-concept:C0441994,
umls-concept:C0678226,
umls-concept:C2911684
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pubmed:issue |
1-2
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pubmed:dateCreated |
2009-9-23
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pubmed:abstractText |
Matrix metalloproteinase 9 (MMP-9) is a Zn(2+)-dependent endopeptidase that degrades some of the components of basement membranes and extracellular matrix and thus participates in leukocyte infiltration during inflammation. In a model of zymosan peritonitis, neutrophil infiltration in MMP-deficient (MMP-9(-/-)) mice was significantly weaker at the time of their maximal influx in wild-type mice (6h). However, during the late stages of peritonitis (24h) an extended accumulation of neutrophils was observed in MMP-9(-/-)versus the wild-type mice. Recently, we reported that the ratio of apoptosis of inflammatory leukocytes is impaired in MMP-9(-/-) mice during late peritonitis and the process depends on COX-1-driven PGE(2). Here we scrutinized the alterations in apoptotic mechanisms by comparisons between MMP-9(-/-) and the wild-type mice. Altered apoptosis occurred only during late (24h) peritonitis and concerned only neutrophils, and not macrophages, mast cells or lymphocytes. Furthermore, expression and activity of caspases was altered in MMP-9(-/-) animals, delayed for caspase-8 and -9, and decreased in the case of caspase-3. Also the expression of Bax/Bcl-2 proteins was changed in MMP-9(-/-) mice. These changes, and in particular the impaired neutrophil apoptosis and weaker caspase-3 activity, were restored by the selective COX-1 inhibition. We conclude that in mice lacking MMP-9 the enhanced COX-1-PGE(2) decreases caspase-3 expression and activity leading to impaired apoptosis of inflammatory neutrophils resulting in abnormal accumulation of the cells at the inflammatory focus. The data also reinforce the notion that MMP-9 is a key enzyme in neutrophil biology.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Bax protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 8,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Ptgs1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrazoles,
http://linkedlifedata.com/resource/pubmed/chemical/SC 560,
http://linkedlifedata.com/resource/pubmed/chemical/Zymosan,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-2-Associated X Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1879-0542
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
22
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pubmed:volume |
126
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
73-82
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pubmed:meshHeading |
pubmed-meshheading:19682497-Animals,
pubmed-meshheading:19682497-Apoptosis,
pubmed-meshheading:19682497-Caspase 3,
pubmed-meshheading:19682497-Caspase 8,
pubmed-meshheading:19682497-Caspase 9,
pubmed-meshheading:19682497-Cyclooxygenase 1,
pubmed-meshheading:19682497-Cyclooxygenase Inhibitors,
pubmed-meshheading:19682497-Female,
pubmed-meshheading:19682497-Flow Cytometry,
pubmed-meshheading:19682497-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:19682497-Immunohistochemistry,
pubmed-meshheading:19682497-Inflammation,
pubmed-meshheading:19682497-Male,
pubmed-meshheading:19682497-Matrix Metalloproteinase 9,
pubmed-meshheading:19682497-Membrane Proteins,
pubmed-meshheading:19682497-Mice,
pubmed-meshheading:19682497-Mice, Inbred C57BL,
pubmed-meshheading:19682497-Mice, Knockout,
pubmed-meshheading:19682497-Microscopy, Fluorescence,
pubmed-meshheading:19682497-Neutrophils,
pubmed-meshheading:19682497-Peritonitis,
pubmed-meshheading:19682497-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:19682497-Pyrazoles,
pubmed-meshheading:19682497-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:19682497-Zymosan,
pubmed-meshheading:19682497-bcl-2-Associated X Protein
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pubmed:year |
2009
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pubmed:articleTitle |
Altered apoptosis of inflammatory neutrophils in MMP-9-deficient mice is due to lower expression and activity of caspase-3.
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pubmed:affiliation |
Department of Evolutionary Immunobiology, Institute of Zoology, Jagiellonian University, ul. Ingardena 6, PL-30-060 Krakow, Poland. ela.kolaczkowska@uj.edu.pl
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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