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H89 Treatment Reduces Intestinal Inflammation and Candida albicans Overgrowth in Mice

Abstract : Deregulation of the dynamic crosstalk between the gut microbiota, intestinal epithelial cells, and immune cells is critically involved in the development of inflammatory bowel disease and the overgrowth of opportunistic pathogens, including the human opportunistic fungus Candida albicans. In the present study, we assessed the effect of N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H89), a protein kinase A inhibitor, on the migration of macrophages to C. albicans through dextran sulphate sodium (DSS)-challenged Caco-2 cells. We also investigated the impact of H89 on intestinal inflammation and C. albicans clearance from the gut, and determined the diversity of the gut microbiota in a murine model of DSS-induced colitis. H89 reduced the migration of macrophages to C. albicans through DSS-challenged Caco-2 cells. In addition, H89 decreased C. albicans viability and diminished the expression of pro-inflammatory cytokines and innate immune receptors in macrophages and colonic epithelial Caco-2 cells. In mice with DSS-induced colitis, H89 attenuated the clinical and histological scores of inflammation and promoted the elimination of C. albicans from the gut. H89 administration to mice decreased the overgrowth of Escherichia coli and Enterococcus faecalis populations while Lactobacillus johnsonii populations increased significantly. Overall, H89 reduced intestinal inflammation and promoted the elimination of C. albicans from the gut.
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https://hal.univ-lille.fr/hal-03283716
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Soumis le : lundi 12 juillet 2021 - 10:29:36
Dernière modification le : mardi 19 octobre 2021 - 11:50:49
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microorganisms-08-02039-v2.pdf
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Distributed under a Creative Commons Paternité 4.0 International License

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Corentin Dumortier, Rogatien Charlet, Ali Bettaieb, Samir Jawhara. H89 Treatment Reduces Intestinal Inflammation and Candida albicans Overgrowth in Mice. Microorganisms, MDPI, 2020, 8 (12), pp.2039. ⟨10.3390/microorganisms8122039⟩. ⟨hal-03283716⟩

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