Organic cation transporter Octn1-mediated uptake of food-derived antioxidant ergothioneine into infiltrating macrophages during intestinal inflammation in mice

Abstract

OCTN1/SLC22A4 is expressed on apical membranes of small intestine, and is involved in gastrointestinal absorption of its substrates, including the food-derived antioxidant ergothioneine (ERGO). ERGO concentration in circulating blood of patients with inflammatory bowel disease (Crohn's disease) is lower than that in healthy volunteers; thus, circulating ERGO is a potential diagnostic marker, although the mechanisms underlying low ERGO concentration in patients are unknown. Here, we focused on intestinal macrophages, which infiltrate sites of inflammation, and examined possible first-pass uptake of ERGO by macrophages. ERGO concentration in blood was lower in mice with dextran sodium sulfate (DSS)-induced colitis than in controls. On the other hand, expression of octn1 gene product and ERGO concentration in intestinal tissues of DSS-treated mice were higher than in controls. Interestingly, lamina propria mononuclear cells (LPMCs) isolated from DSS-treated mice contained ERGO and showed [(3)H]ERGO uptake and Octn1 expression, whereas ERGO was undetectable in LPMCs of control mice. Functional expression of OCTN1 was also confirmed in LPS-stimulated human macrophage-like cell line, THP-1. In conclusion, OCTN1 is functionally expressed on activated intestinal macrophages, and ERGO uptake into these immune cells could contribute at least in part to the altered disposition of ERGO in intestinal inflammation.

Keywords: Crohn's disease; DSS colitis model mice; Ergothioneine; Macrophages; OCTN1.