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Deletion Of The Meprin Metalloprotease βGene Protects Against Intestinal Inflammation In Mice
Author(s) -
Banerjee Sanjita,
Gailey Ryan D,
Bradley S Gaylen,
Bond Judith S
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a533-b
Subject(s) - proteases , inflammation , metalloproteinase , biology , immune system , knockout mouse , downregulation and upregulation , brush border , ileum , microbiology and biotechnology , immunology , gene , matrix metalloproteinase , biochemistry , enzyme , vesicle , membrane
Inflammatory bowel diseases results in damage to the intestinal epithelium, and are caused by ill‐defined genetic and environmental factors that affect host‐microbe interactions and production of inflammatory mediators. Proteases, by activating and/or degrading cytokines, are thought to play an important role in maintaining the delicate balance in the gut. Meprins are membrane‐bound and secreted metalloproteases that are enriched in the brush border membranes of the ileum and in leukocytes. They are capable of activating and degrading cytokines as well as proteins. To investigate the role of meprins in intestinal immune responses, inflammation was induced by oral administration of dextran sulphate sodium (DSS). The results showed that wild‐type mice (C57Bl/6 x 129J) had a more severe reaction to DSS than meprin ( null mice on the same genetic background, as determined by loss of body weight, rectal bleeding, and mortality. This implies that the absence of meprin ( renders protection to the host gut against the damage caused by DSS. Our initial data also indicate that the bacterial flora in the gut is different in the meprin ( null mice compared to wild‐type mice, which implies that bacterial interactions or adhesion are altered in the null mouse intestine. Preliminary studies also indicate that Toll‐like receptor‐6 mRNA is upregulated in the meprin ( knockout mouse. These studies indicate that meprin ( plays an active role in intestinal pathophysiology. (This work is funded by NIH DK 19691).