Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
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Query: UMLS:C0031154 (
peritonitis
)
15,372
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Matrix metalloproteinase 9
(
MMP-9
) belongs to a family of zinc-dependent endopeptidases. As a consequence of its ability to cleave structural extracellular matrix molecules, mammalian
MMP-9
is associated with vital inflammatory processes such as leucocyte migration and tissue remodelling and regeneration. Interestingly,
MMP-9
genes have been identified in fish, but functional data are still limited and focus on the involvement of
MMP-9
in embryonic development, reproduction and post-mortem tenderization. Here, we describe the involvement of
MMP-9
in the innate immunity of carp. In carp,
MMP-9
was most notably expressed in classical fish immune organs and in peritoneal and peripheral blood leucocytes, indicating a role of
MMP-9
in immune responses. In our well-characterized zymosan-induced
peritonitis
model for carp, we analysed expression of the
MMP-9
gene and the gelatinolytic levels of both pro- and activated forms of
MMP-9
. The biphasic profile of
MMP-9
mRNA expression indicated involvement during the initial phase of inflammation and during the later phase of tissue remodelling. Also, in vitro stimulation of carp phagocytes with lipopolysaccharide or concanavalin A increased
MMP-9
gene expression, with a peak at 24 hr. The increase of
MMP-9
mRNA correlated with the peak of
MMP-9
gelatinolytic level in culture supernatants. These results provide evidence for an evolutionarily conserved and relevant role of
MMP-9
in the innate immune response.
...
PMID:Expression profiles of matrix metalloproteinase 9 in teleost fish provide evidence for its active role in initiation and resolution of inflammation. 1855 54
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.
...
PMID:Altered apoptosis of inflammatory neutrophils in MMP-9-deficient mice is due to lower expression and activity of caspase-3. 1968 97
