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Verbeke, S. M.1; Gotteland, M.1; Cruchet, S. A.1; Calderón, J. F.1; Ríos, G.2; Brunser, O.1
1Gastroenterology, Institute of Nutrition and Food Technology, 2Gastroenterology, Hospital Exequiel Gonzalez Cortes, Santiago, Chile
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Introduction: Collagen type IV, laminin and fibronectin are decreased in the basement membrane of the intestinal ephitelium of the intestinal mucosa of coeliac patients; there are also disturbances of the disposition of lamina propria miofibroblasts (MF) evinced by changes in their smooth muscle a-actin. These basement membrane proteins and the enzymes that degrade them (metalloproteinases, MMPs) are synthetized by the MF. The equilibrium between the synthesis and degradation of the extra-cellular matrix contributes to maintain the normal architecture of the mucosa. The mucosal lesion in coeliac disease may be explained by disturbances of the MF or their various products triggered by dietary gliadin. One of the aims of this study was to evaluate the changes of MMPs distribution in the mucosa of coeliac patients; the second aim was to evaluate the response of MF with respect to MMPs secretion and activity to stimulation with IFN-g and TNF-a.
Methods: MF from small intestinal biopsies from coeliac patients and controls and the respective condition medium with and without the stimuli provided by IFN-g and TNF-a were cultured. The activity of MMP-2 was evaluated by zymography and the concentration of MMP-3 by ELISA in the condicioned media by the MF. The distribution of MMP-1 and MMP-3 was evaluated by immunohistochemistry in tissue sections from biopsies from the same individuals.
Results: MMP-3 concentration in the conditioned media of the controls did not show differences before or after cytokine stimulation while in the celiac patients MMP-3 concentration seems to correlate with the type and concentration of the stimulating cytokines. MMP-2 activity was higher in the coeliacs than in the control; both TNF-a and IFN-g stimulated in dose-dependent fashion the activity of this MMP. The immunohistochemical staining for MMP-1 and MMP-3 was more intense in the coeliac patients than in the controls.
Conclusion: The morphological alterations of the intestinal mucosa in coeliac disease may be related to changes, mainly increases, in the concentrations and the activities of the MMPs originated by inflammatory and immunological processes induced by gliadin in susceptible individuals.
© 2004 Lippincott Williams & Wilkins, Inc.
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