BACKGROUND & AIMS: Activated proteases such as plasmin

and matrix metalloproteinases (MMPs) are activated in intestinal

tissues of patients with active inflammatory bowel

diseases. We investigated the effect of plasmin on the progression

of acute colitis. METHODS: Colitis was induced in

Mmp9-/-, Plg-/-, and C57BL/6 (control) mice by the administration

of dextran sulfate sodium, trinitrobenzene sulfonic acid,

or CD40 antibody. Plasmin was inhibited in control mice by

intraperitoneal injection of YO-2, which blocks its active site.

Mucosal and blood samples were collected and analyzed by

reverse-transcription polymerase chain reaction and immunohistochemical

analyses, as well as for mucosal inflammation

and levels of cytokines and chemokines. RESULTS: Circulating

levels of plasmin were increased in mice with colitis, compared

with controls. Colitis did not develop in control mice injected

with YO-2 or in Plg-/- mice. Colons from these mice had reduced

infiltration of Gr1. neutrophils and F4/80. macrophages, and

reduced levels of inflammatory cytokines and chemokines.

Colonic inflammation and colitis induction required activation

of endogenous MMP9. After colitis induction, mice given YO-2,

Plg-/- mice, and Mmp9-/- mice had reduced serum levels of tumor

necrosis factor and C-X-C motif chemokine ligand 5,

compared with control mice.

Title

Gastroenterology

Publisher

science direct

Publisher Country

United States of America

Publication Type

Prtinted only

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Year

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