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.

• Authors: Takuya Shimizu, Yusuke Masuo, Saki Takahashi, Noritaka Nakamichi, Yukio Kato
• Journal: Drug metabolism and pharmacokinetics (Drug Metab Pharmacokinet) Vol. 30 Issue 3 Pg. 231-9 (Jun 2015) ISSN: 1880-0920 [Electronic] England
• PMID: 26003890 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Antioxidants
• Carrier Proteins
• Lipopolysaccharides
• Membrane Proteins
• Organic Cation Transport Proteins
• SLC22A4 protein, human
• Slc22a4 protein, mouse
• Symporters
• Ergothioneine

Topics

• Animals
• Antioxidants (metabolism)
• Blotting, Western
• Carrier Proteins (genetics)
• Cell Line
• Colitis (genetics, immunology, metabolism)
• Disease Models, Animal
• Epithelial Cells (drug effects, immunology, metabolism)
• Ergothioneine (blood, metabolism, urine)
• Flow Cytometry
• Food
• Humans
• Immunohistochemistry
• Intestinal Mucosa (metabolism)
• Lipopolysaccharides (pharmacology)
• Macrophages (drug effects, immunology, metabolism)
• Male
• Membrane Proteins (genetics)
• Mice, Inbred C57BL
• Mice, Knockout
• Nutritional Physiological Phenomena
• Organic Cation Transport Proteins (genetics)
• Symporters