Role of the Aryl Hydrocarbon Receptor (AhR) in Mediating the Effects of Coffee in the Colon.

Autor: Chapkin RS; Departments of Nutrition and Biochemistry & Biophysics Texas A&M University, College Station, TX, 77843, USA., Davidson LA; Departments of Nutrition and Biochemistry & Biophysics Texas A&M University, College Station, TX, 77843, USA., Park H; Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, 77843, USA., Jin UH; Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, 77843, USA., Fan YY; Departments of Nutrition and Biochemistry & Biophysics Texas A&M University, College Station, TX, 77843, USA., Cheng Y; Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, 77843, USA., Hensel ME; Department of Veterinary Pathobiology, Texas A&M University, College Station, TX, 77843, USA., Landrock KK; Departments of Nutrition and Biochemistry & Biophysics Texas A&M University, College Station, TX, 77843, USA., Allred C; Departments of Nutrition and Biochemistry & Biophysics Texas A&M University, College Station, TX, 77843, USA., Menon R; Department of Chemical Engineering, Texas A&M University, College Station, TX, 77843, USA., Klemashevich C; Department of Chemical Engineering, Texas A&M University, College Station, TX, 77843, USA., Jayaraman A; Department of Chemical Engineering, Texas A&M University, College Station, TX, 77843, USA., Safe S; Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, 77843, USA.
Jazyk: angličtina
Zdroj: Molecular nutrition & food research [Mol Nutr Food Res] 2021 Oct; Vol. 65 (20), pp. e2100539. Date of Electronic Publication: 2021 Aug 31.
DOI: 10.1002/mnfr.202100539
Abstrakt: Scope: This study investigates the mechanism of action and functional effects of coffee extracts in colonic cells, on intestinal stem cell growth, and inhibition of dextran sodium sulfate (DSS)-induced intestinal barrier damage in mice.
Methods and Results: Aqueous coffee extracts induced Ah receptor (AhR) -responsive CYP1A1, CYP1B1, and UGT1A1 gene expression in colon-derived Caco2 and YAMC cells. Tissue-specific AhR knockout (AhR f/f x Lgr5-GFP-CreERT2 x Villin-Cre), wild-type (Lgr5-CreERT2 x Villin-Cre) mice are sources of stem cell enriched organoids and both coffee extracts and norharman, an AhR-active component of these extracts inhibited stem cell growth. Coffee extracts also inhibit DSS-induced damage to intestinal barrier function and DSS-induced mucosal inflammatory genes such as IL-6 and TGF-β1 in wild-type (AhR +/+ ) but not AhR -/- mice. In contrast, coffee does not exhibit protective effects in intestinal-specific AhR knockout mice. Coffee extracts also enhanced overall formation of AhR-active microbial metabolites.
Conclusions: In colon-derived cells and in the mouse intestine, coffee induced several AhR-dependent responses including gene expression, inhibition of intestinal stem cell-enriched organoid growth, and inhibition of DSS-induced intestinal barrier damage. We conclude that the anti-inflammatory effects of coffee in the intestine are due, in part, to activation of AhR signaling.
(© 2021 Wiley-VCH GmbH.)
Databáze: MEDLINE
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