Calprotectin protects against experimental colonic inflammation in mice.

Aranda CJ, Ocón B, Arredondo-Amador M, Suárez MD, Zarzuelo A, Chazin WJ, Martínez-Augustin O, Sánchez de Medina F
Br J Pharmacol. 2018 175 (19): 3797-3812

PMID: 30007036 · PMCID: PMC6135788 · DOI:10.1111/bph.14449

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 μg·day ) by the intrarectal or by i.p. injection (50 μg·day 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 TNFα 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 NFκB.

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.

© 2018 The British Pharmacological Society.

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