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A Role For Meprin‐ α In A Model Of Inflammatory Bowel Disease
Author(s) -
Banerjee Sanjita,
Fitzpatrick Leo R,
Bradley S Gaylen,
Bond Judith S
Publication year - 2007
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.21.5.a278-d
Subject(s) - inflammatory bowel disease , inflammation , knockout mouse , pathogenesis , ileum , nitric oxide , colitis , wild type , immunology , medicine , in vivo , pathology , biology , disease , biochemistry , gene , receptor , microbiology and biotechnology , mutant
Inflammatory Bowel Diseases (IBDs) are clinically heterogeneous intestinal diseases characterized by damage to the intestinal epithelium and chronic inflammation of the ileum and colon. Data from our laboratory and those of others have led to the hypothesis that meprins, metalloproteases of intestinal epithelial cells and leukocytes, have an active role in the pathogenesis of IBDs. To study the role of meprins in vivo , meprin α knockout (KO) mice were generated by targeted disruption of the Mep‐1 α gene, on chromosome 17. The results indicate that meprin αKO mice (on C57BL/6x129J background) have significantly smaller litters than their wild‐type counterparts. To investigate the role of meprins in IBDs, inflammation was induced in 8 to 9 week old male wild‐type and meprin αKO mice by ad libitum administration of 3.5% dextran sulfate sodium (DSS) for 4 days, followed by normal drinking water on days 5 to 7. All treated mice lost weight, developed rectal bleeding and showed signs of diarrhea. The summative disease activity index showed an earlier and more severe response in αKO mice than in the wild‐type mice. The αKO mice had greater colon injury, as monitored histologically, and elevated levels of myeloperoxidase, nitric oxide and IL‐18 compared to wild‐type mice. These data indicate a beneficial role of meprin α in the pathophysiology of IBD. [Funded by NIH DK 19691].