期刊
EUROPEAN JOURNAL OF MICROBIOLOGY AND IMMUNOLOGY
卷 1, 期 4, 页码 302-310出版社
AKADEMIAI KIADO ZRT
DOI: 10.1556/EuJMI.1.2011.4.6
关键词
matrixmetalloproteinases; gelatinasesA and B; acute DSS colitis; innate immunity; host responses to inflammation; gut microbiota; E. coli
类别
资金
- German Research Foundation (DFG) [GO363/12-1, SFB633, TP A7, TP Z1, TP A12, TP B6]
- German Federal Ministry of Education and Research (BMBF) [TP1.1, TP 8.2]
Expression of gelatinases A and B, also referred to matrixmetalloproteinases (MMP)-2 and-9, respectively, is increased in inflamed tissues of experimental intestinal inflammation and humans with inflammatory bowel disease (IBDs). Given that we recently reported that treatment with the selective gelatinase inhibitor RO28-2653 ameliorates acute dextrane sulfate sodium (DSS) colitis, we asked whether gelatinase A or B expression is pivotal in mediating large intestinal inflammation. Results from our study reveal that symptoms of acute DSS colitis as well as histopathological colonic changes were ameliorated in MMP-2-, but not MMP-9-deficient mice, and were paralleled by a diminished influx of immune cells. In MMP-2-deficient mice, we observed lower expression of pro-inflammatory cytokines including interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and IL-6 in colonic biopsies and less overgrowth of the colonic lumen by potentially pro-inflammatory enterobacteria from the commensal gut microbiota. We conclude that rather MMP-2 than MMP-9 is causative for the establishment of DSS colitis in mice. The discrepancy of these data to prior reports might be due to substantial differences in the intestinal microbiota composition of the mice bred at different animal facilities impacting susceptibility to inflammatory stimuli. Consequently, a detailed survey of the gut microbiota should be implemented in immunological/ inflammatory studies in the future in order to allow comparison of data from different facilities.
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