Kategorie: Onkologická diagnostika
Číslo abstraktu: 001p
Aim: In this study, we aimed to analyse the functional role of MMP19 in intestinal inflammation by using MMP19-deficient mice in a mouse model of chemically-induced colitis.
Material and methods: Dextran sodium sulphate (DSS) was administered to age-matched male wild-type (WT) and MMP-19 deficient mice (C57Bl/6 background) at a concentration of 2% (w/v) in drinking water for 6 days to induce acute colitis. For analysing the healing process mice were given 2% DSS for 5 days followed by a 10 day recovery period using normal drinking water. The administration of two cycles of DSS (2% DSS for 4 days, 10 days water) results in chronic colitis. Colitis severity was assessed by changes in body weight, stool consistency and occult bleeding. Furthermore, colon length was determined and histological analysis of its proximal, middle and distal parts was performed. Cytokine concentrations (IL-6, IL-1â, KC, MCP-1) in plasma and supernatants of colon tissue explants were measured by Luminex.
Results: During the course of DSS-induced acute colitis, the MMP19-deficient mice lost significantly more weight than the WT mice (22%±5% vs. 12%±3%, p<0.08). Also, the disease activity index (DAI) that included also the severity of diarrhoea and the amount of blood in stool was remarkably higher in MMP19-deficient mice. Histologically, the MMP19-deficient mice showed reduced infiltration of neutrophils into the colonic tissue during the course of colitis but increased lesion extent, ulceration and oedema. The differences between WT and knockout mice were even more striking in the recovery phase of the colitis as MMP19-deficient animals showed only 65% survival. During the chronic colitis just 50% survived and they did not regain their initial weight. MMP19-deficient animals showed elevated levels of pro-inflammatory cytokines in blood plasma and supernatants of ex vivo cultures of colonic tissues during all phases of colitis.
Conclusion: The exacerbation of the colitis in the MMP19-deficient mice together with elevated concentrations of pro-inflammatory cytokines derived from colonic tissue suggests that MMP19 plays an essential role in maintenance of intestinal homeostasis. This may have important implications for the two major inflammatory conditions of the intestine in humans, Crohn‘s disease and ulcerative colitis.
Datum přednesení příspěvku: 29. 4. 2011