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.
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SLC22A4 and its homologues have significant specificity for ERG and weak activity for various drugs.
“Subsequent work(87,169–172) has confirmed and reinforced this view of SLC22A4 and its homologues(173) as having significant specificity for ERG, and weak activity for various drugs(174–177).”
From The biology of ergothioneine, an antioxidant nutraceutical (2020) · cites this paper as [173]
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- Authors
- Shimizu, T., Masuo, Y., Takahashi, S., Nakamichi, N., & Kato, Y.
- Affiliations
- Kanazawa University (JP)
- Corresponding author
- Kato, Yukio
- Venue
- Drug Metabolism and Pharmacokinetics
- Publisher
- Elsevier BV
- Published
- 2015-06
- Volume
- 30
- Issue
- 3
- Pages
- 231-239
- ISSN
- 1347-4367 (ISSN-L)
- OpenAlex
- W2071190006
- Cited by
- 45
- References
- 40
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 1 · 2023: 5 · 2022: 5 · 2021: 7 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 1 · 2015: 1
- FWCI
- 1.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Drug Metabolism and Pharmacokinetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Science and Culture of Japan (24390040)
- Takeda Science Foundation
- Shimadzu Foundation
- Hoansha Foundation
- National Institute of Biomedical Innovation
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Keywords
- ergothioneine, OCTN1, SLC22A4, intestinal macrophages, intestinal inflammation, DSS-induced colitis, inflammatory bowel disease, Crohn's disease, lamina propria mononuclear cells, THP-1 macrophages, dietary antioxidants, biomarkers
- MeSH terms
- Animals, Antioxidants, Carrier Proteins, Cell Line, Colitis, Disease Models, Animal, Epithelial Cells, Ergothioneine, Flow Cytometry, Food, Humans, Immunohistochemistry, Intestinal Mucosa, Lipopolysaccharides, Macrophages, Male, Membrane Proteins, Mice, Inbred C57BL, Nutritional Physiological Phenomena, Blotting, Western, Mice, Knockout, Organic Cation Transport Proteins, Symporters
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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