Linked Life Data

19175797

Source:http://linkedlifedata.com/resource/pubmed/id/19175797

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1 Suppl
pubmed:dateCreated
2009-9-10
pubmed:abstractText
Matrix metalloproteinase-9 (MMP-9)/gelatinase B plays an important role in neutrophil infiltration during inflammation and cyclooxygenases (COX-1 and COX-2) and their products are important regulators of inflammation. Recently, we reported that a genetic lack of MMP-9 impairs neutrophil infiltration during early zymosan-induced peritonitis but at later stages (> 24 hr) neutrophils persist in the peritoneal cavity. Here we show that this is the result of impaired apoptosis of MMP-9(-/-)-derived leucocytes. As enhanced COX-1 expression was reported in MMP-9(-/-) mice, we evaluated the hypothesis that altered COX expression induced the above phenomenon as COX-dependent prostaglandins can act either anti-apoptotically (PGE(2)) or pro-apoptotically (PGD(2)). The current data demonstrate that messenger RNA and protein expression of both COX isoforms and their activities are increased in MMP-9(-/-) mice during late peritonitis. Application of selective COX inhibitors revealed enhanced COX-1-dependent PGE(2) production and impaired COX-2-dependent PGD(2) synthesis in MMP-9(-/-) mice. Most importantly, inhibition of COX-1 abolished prolonged neutrophil accumulation in the peritoneal cavity of MMP-9(-/-) mice and increased apoptosis of inflammatory leucocytes. Similarly, weaker apoptosis of MMP-9(-/-) bone marrow neutrophils treated in vitro with zymosan was reversed by COX-1 inhibition. In conclusion, enhanced COX-1 expression is responsible for persistent neutrophil presence in the peritoneum of MMP-9(-/-) mice because of increased synthesis of anti-apoptotic PGE(2). In non-transgenic mice, however, inflammatory leucocytes die apoptotically in the late stages of peritonitis as a result of COX-2-dependent PGD(2) activity. Overall, we show a dependence of COX expression on the presence of MMP-9.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 1, http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2, http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone, http://linkedlifedata.com/resource/pubmed/chemical/DuP 697, http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 9, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin D2, http://linkedlifedata.com/resource/pubmed/chemical/Ptgs1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Ptgs2 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Pyrazoles, http://linkedlifedata.com/resource/pubmed/chemical/SC 560, http://linkedlifedata.com/resource/pubmed/chemical/Thiophenes, http://linkedlifedata.com/resource/pubmed/chemical/Zymosan
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1365-2567
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
128
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
e262-74
pubmed:dateRevised
2010-9-2
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Increased cyclooxygenase activity impairs apoptosis of inflammatory neutrophils in mice lacking gelatinase B/matrix metalloproteinase-9.
pubmed:affiliation
Department of Evolutionary Immunobiology, Institute of Zoology, Jagiellonian University, Krakow, Poland. ela.kolaczkowska@uj.edu.pl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't