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Organic cation transporter Octn1-mediated uptake of food-derived antioxidant ergothioneine into infiltrating macrophages during intestinal inflammation in mice.
Drug Metab Pharmacokinet. 2015 Jun; 30(3):231-9.DM

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+Show Affiliations

Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-1192, Japan.Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-1192, Japan.Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-1192, Japan.Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-1192, Japan.Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-1192, Japan. Electronic address: ykato@p.kanazawa-u.ac.jp.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26003890

Citation

Shimizu, Takuya, et al. "Organic Cation Transporter Octn1-mediated Uptake of Food-derived Antioxidant Ergothioneine Into Infiltrating Macrophages During Intestinal Inflammation in Mice." Drug Metabolism and Pharmacokinetics, vol. 30, no. 3, 2015, pp. 231-9.
Shimizu T, Masuo Y, Takahashi S, et al. Organic cation transporter Octn1-mediated uptake of food-derived antioxidant ergothioneine into infiltrating macrophages during intestinal inflammation in mice. Drug Metab Pharmacokinet. 2015;30(3):231-9.
Shimizu, T., Masuo, Y., Takahashi, S., Nakamichi, N., & Kato, Y. (2015). Organic cation transporter Octn1-mediated uptake of food-derived antioxidant ergothioneine into infiltrating macrophages during intestinal inflammation in mice. Drug Metabolism and Pharmacokinetics, 30(3), 231-9. https://doi.org/10.1016/j.dmpk.2015.02.003
Shimizu T, et al. Organic Cation Transporter Octn1-mediated Uptake of Food-derived Antioxidant Ergothioneine Into Infiltrating Macrophages During Intestinal Inflammation in Mice. Drug Metab Pharmacokinet. 2015;30(3):231-9. PubMed PMID: 26003890.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Organic cation transporter Octn1-mediated uptake of food-derived antioxidant ergothioneine into infiltrating macrophages during intestinal inflammation in mice. AU - Shimizu,Takuya, AU - Masuo,Yusuke, AU - Takahashi,Saki, AU - Nakamichi,Noritaka, AU - Kato,Yukio, Y1 - 2015/02/25/ PY - 2014/11/22/received PY - 2015/02/10/revised PY - 2015/02/12/accepted PY - 2015/5/25/entrez PY - 2015/5/25/pubmed PY - 2016/3/22/medline KW - Crohn's disease KW - DSS colitis model mice KW - Ergothioneine KW - Macrophages KW - OCTN1 SP - 231 EP - 9 JF - Drug metabolism and pharmacokinetics JO - Drug Metab Pharmacokinet VL - 30 IS - 3 N2 - 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. SN - 1880-0920 UR - https://www.unboundmedicine.com/medline/citation/26003890/Organic_cation_transporter_Octn1_mediated_uptake_of_food_derived_antioxidant_ergothioneine_into_infiltrating_macrophages_during_intestinal_inflammation_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1347-4367(15)00017-8 DB - PRIME DP - Unbound Medicine ER -