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      Intestinal Expression of Genes Encoding Inflammatory Mediators and Gelatinases During Arcobacter Butzleri Infection of Gnotobiotic Il-10 Deficient Mice

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          Abstract

          We have previously shown that Arcobacter butzleri induces intestinal, extra-intestinal, and systemic immune responses in perorally infected gnotobiotic IL-10 –/– mice in a strain-dependent fashion. Here, we present a comprehensive survey of small and large intestinal expression profiles of inflammatory and regulatory mediators as well as of the matrix-degrading gelatinases MMP-2 and MMP-9 following murine A. butzleri infection. Gnotobiotic IL-10 –/– mice were infected with A. butzleri strains CCUG 30485 or C1 of human and chicken origin, respectively. At day 6 following A. butzleri infection, mucin-2 mRNA, an integral part of the intestinal mucus layer, was downregulated in the colon, whereas TNF and IL-23p19 mRNA were upregulated in the ileum. Furthermore, IFN-γ, IL-17A, IL-1β, and IL-22 mRNA were upregulated in both colonic and ileal ex vivo biopsies at day 6 post strain CCUG 30485 infection. These changes were accompanied by downregulated colonic MMP-9 levels, whereas both MMP-2 and MMP-9 mRNA were upregulated in the ileum. In conclusion, these data indicate that A. butzleri infection induces changes in the expression of genes involved in pro-inflammatory and regulatory immune responses as well as in tissue degradation.

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          Most cited references26

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          The biological functions of T helper 17 cell effector cytokines in inflammation.

          T helper 17 (Th17) cells belong to a recently identified T helper subset, in addition to the traditional Th1 and Th2 subsets. These cells are characterized as preferential producers of interleukin-17A (IL-17A), IL-17F, IL-21, and IL-22. Th17 cells and their effector cytokines mediate host defensive mechanisms to various infections, especially extracellular bacteria infections, and are involved in the pathogenesis of many autoimmune diseases. The receptors for IL-17 and IL-22 are broadly expressed on various epithelial tissues. The effector cytokines of Th17 cells, therefore, mediate the crucial crosstalk between immune system and tissues, and play indispensable roles in tissue immunity.
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            Colorectal cancer in mice genetically deficient in the mucin Muc2.

            The gastrointestinal tract is lined by a layer of mucus comprised of highly glycosylated proteins called mucins. To evaluate the importance of mucin in intestinal carcinogenesis, we constructed mice genetically deficient in Muc2, the most abundant secreted gastrointestinal mucin. Muc2-/- mice displayed aberrant intestinal crypt morphology and altered cell maturation and migration. Most notably, the mice frequently developed adenomas in the small intestine that progressed to invasive adenocarcinoma, as well as rectal tumors. Thus, Muc2 is involved in the suppression of colorectal cancer.
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              Matrix Metalloproteinases: A Review

              Matrix metalloproteinases (MMPs) are a family of nine or more highly homologous Zn(++)-endopeptidases that collectively cleave most if not all of the constituents of the extracellular matrix. The present review discusses in detail the primary structures and the overlapping yet distinct substrate specificities of MMPs as well as the mode of activation of the unique MMP precursors. The regulation of MMP activity at the transcriptional level and at the extracellular level (precursor activation, inhibition of activated, mature enzymes) is also discussed. A final segment of the review details the current knowledge of the involvement of MMP in specific developmental or pathological conditions, including human periodontal diseases.
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                Author and article information

                Journal
                Eur J Microbiol Immunol (Bp)
                Eur J Microbiol Immunol (Bp)
                EUJMI
                European Journal of Microbiology & Immunology
                Akadémiai Kiadó (Budapest )
                2062-509X
                2062-8633
                28 March 2016
                March 2016
                : 6
                : 1
                : 56-66
                Affiliations
                [1 ] Department of Microbiology and Hygiene, Charité – University Medicine Berlin , Berlin, Germany
                [2 ]Institute of Food Hygiene, Free University Berlin , Berlin, Germany
                Author notes
                * Charité – University Medicine Berlin, CC5, Department of Microbiology and Hygiene, Campus Benjamin Franklin, FEM, Garystr. 5, D-14195 Berlin, Germany; +49-30-450524318; markus.heimesaat@ 123456charite.de

                Financial disclosure, grant support

                This work was supported by grants from the German Research Foundation (DFG) to S.B. (SFB633, TP A7) and M.M.H. (SFB633, TP B6) and from the German Federal Ministery of Education and Research (BMBF) to S.B. (TP1.1).

                The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article.

                Competing interests

                The authors have declared that no competing interests exist.

                Article
                10.1556/1886.2016.00005
                4838986
                27141315
                26329f19-3c34-49a0-91d2-d1dbe9f615fd
                © The Author(s)

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 07 March 2016
                : 08 March 2016
                Page count
                Figures: 10, Tables: 0, Equations: 0, References: 37, Pages: 11
                Categories
                Original Article

                arcobacter butzleri,campylobacterales,il-23/th17 axis,il-22/il-18 axis,pro-inflammatory immune responses,intestinal tract,gnotobiotic il-10–/– mouse infection model,gelatinases,host defence,mucosal immunology

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