Gastroenterology
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Randomized Controlled Trial Clinical Trial
Inhibition of stress-activated MAP kinases induces clinical improvement in moderate to severe Crohn's disease.
We investigated if inhibition of mitogen-activated protein kinases (MAPKs) was beneficial in Crohn's disease. ⋯ Inflammatory MAPKs are critically involved in the pathogenesis of Crohn's disease and their inhibition provides a novel therapeutic strategy.
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In pancreatitis-associated lung injury, neutrophils (PMN) access the lung by migration through endothelial basement membranes. We hypothesize that degeneration of the basement membrane by specific PMN-produced matrix metalloproteinases (MMPs) may facilitate this process. ⋯ MMP-9 secretion by PMN can be stimulated by trypsin and proinflammatory cytokines and increases in pancreatitis in proportion to its severity. MMP inhibition reduces PMN transmigration and reduces resultant alveolar-capillary leakage. These findings suggest an important role for MMP-9 from PMN in the pathogenesis of pancreatitis-associated lung injury.