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Calprotectin protects against experimental colonic inflammation in mice.

ABSTRACT: BACKGROUND AND PURPOSE:Calprotectin is a heterodimer composed of two myeloid-related proteins, S100A8 and S100A9, that is abundant in neutrophils and monocytes/macrophages. Faecal levels of calprotectin are used routinely to monitor inflammatory bowel disease activity. EXPERIMENTAL APPROACH:We aimed to assess the role of calprotectin in intestinal inflammation, using the dextran sulfate sodium model of colitis in mice. Calprotectin was administered (50 or 100 ?g·day-1 ) by the intrarectal or by i.p. injection (50 ?g·day-1 only). The condition of the mice was characterized by morphological and biochemical methods. KEY RESULTS:Intrarectal calprotectin protected significantly against colitis, as shown by lower levels of macroscopic and microscopic damage, colonic myeloperoxidase activity and decreased expression of TNF? and toll-like receptor 4. IL-17 production by spleen and mesenteric lymph node cells was reduced. Calprotectin had no effect on body weight loss or colonic thickening. There were no effects of calprotectin after i.p. injection. Calprotectin had virtually no effects in control, non-colitic mice. Calprotectin had almost no effect on the colonic microbiota but enhanced barrier function. Treatment of rat IEC18 intestinal epithelial cells in vitro with calprotectin induced output of the chemokines CXL1 and CCL2, involving the receptor for advanced glycation end products- and NF?B. CONCLUSION AND IMPLICATIONS:Calprotectin exerted protective effects in experimental colitis when given by the intrarectal route, by actions that appear to involve effects on the epithelium.

SUBMITTER: Aranda CJ

PROVIDER: S-EPMC6135788 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Calprotectin protects against experimental colonic inflammation in mice.

Aranda Carlos J CJ Ocón Borja B Arredondo-Amador María M Suárez María Dolores MD Zarzuelo Antonio A Chazin Walter J WJ Martínez-Augustin Olga O Sánchez de Medina Fermín F

British journal of pharmacology 20180902 19

<h4>Background and purpose</h4>Calprotectin is a heterodimer composed of two myeloid-related proteins, S100A8 and S100A9, that is abundant in neutrophils and monocytes/macrophages. Faecal levels of calprotectin are used routinely to monitor inflammatory bowel disease activity.<h4>Experimental approach</h4>We aimed to assess the role of calprotectin in intestinal inflammation, using the dextran sulfate sodium model of colitis in mice. Calprotectin was administered (50 or 100 μg·day<sup>-1</sup> ) ...[more]

PMID: 30007036

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Project description:Background: Ulcerative colitis is characterized by relapsing and remitting mucosal inflammation. Bovine lactoferrin (BL) is a multifunctional protein that could regulate the intestinal flora and has anti-inflammatory effects. The aim of this study was to investigate the therapeutic effect of BL on colitis. Methods: Dextran sulfate sodium salt (DSS) was utilized to establish a mouse model of colitis. BL was administered to treat DSS mice. The weight, the activity, and fecal status of the mice were recorded every day. Disease activity index was calculated. After the mice were euthanized, the colon length was measured. Hematoxylin and eosin staining was used to observe the pathological changes of the colon, and histological activity index was calculated. The myeloperoxidase (MPO) activity of colon tissue was measured. Western blot and immunohistochemistry were used to detect the expressions of Claudin-1, Occludin, and ZO-1. The expressions of IL-1β, IL-6, IL-10, TNF-α, and TGF-β in colon tissue were detected by ELISA. The protein expressions of MUC2, Reg3γ, β-defensin (HBD-2), and cAMP were detected by immunofluorescence (IF). 16S rDNA sequencing determined the type and structure of intestinal flora. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) measured the metabolites of the intestinal flora. Results: Compared with the DSS group, the mice's weight in the BL group was higher and the length of the colon was longer. At the 14th day, MPO activity was higher in the BL group. The expressions of Claudin-1, Occludin, and ZO-1 in the colon were up-regulated in the BL group compared with the DSS group. The expressions of IL-1β, IL-6, and TNF-α were lower. The expressions of IL-10 and TGF-β were higher. IF showed that the expressions of MUC2 and β-defensin (HBD-2) were down-regulated, and the expressions of Reg3γ and cAMP were up-regulated. The 16S rDNA sequencing results showed that the alpha diversity and beta diversity were notably changed in the DSS mice treated with BL. Metabolomics results showed that BL changed purine metabolism in the DSS mice. Conclusion: BL alleviated colitis in mice by improving the inflammatory response and the structure of the colon barrier in the colon. BL changed the composition and metabolites of the intestinal flora. Thus, BL might be an effective nutritional supplement for colitis treatment.

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Calprotectin protects against experimental colonic inflammation in mice.

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Calprotectin protects against experimental colonic inflammation in mice.

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