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Title: 4-Hydroxydocosahexaenoic acid, a potent peroxisome proliferator-activated receptor {gamma} agonist alleviates the symptoms of DSS-induced colitis

Abstract

(5E,7Z,10Z,13Z,16Z,19Z)-4-Hydroxy-5,7,10,13,16,19-docosahexaenoic acid (4-OHDHA) is a potential agonist of peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}) and antidiabetic agent as has been previously reported. As PPAR{gamma} agonists may also have anti-inflammatory functions, in this study, we investigated whether 4-OHDHA has an inhibitory effect on expression of inflammatory genes in vitro and whether 4-OHDHA could relieve the symptoms of dextran sodium sulfate (DSS)-induced colitis in a murine model of inflammatory bowel disease. 4-OHDHA inhibited production of nitric oxide and expression of a subset of inflammatory genes including inducible nitric oxide synthase (Nos2/iNOS) and interleukin 6 (Il6) by lipopolysaccharide (LPS)-activated macrophages. In addition, 4-OHDHA-treated mice when compared to control mice not receiving treatment recovered better from the weight loss caused by DSS-induced colitis. Changes in disease activity index (DAI) of 4-OHDHA-treated mice were also more favorable than for control mice and were comparable with mice treated with a typical anti-inflammatory-drug, 5-aminosalichylic acid (5-ASA). These results suggest that 4-OHDHA has potentially clinically useful anti-inflammatory effects mediated by suppression of inflammatory gene expression.

Authors:
 [1]; ;  [2]; ;  [3]; ;  [4];  [3];  [5];  [2];  [6]
  1. Laboratory of Drug Design and Medicinal Chemistry, Showa Pharmaceutical University, 3-3165 Higashi-Tamagawagakuen, Machida, Tokyo 194-8543 (Japan)
  2. Division of Translational Research, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1241 (Japan)
  3. Division of Functional Genomics and Systems Medicine, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1241 (Japan)
  4. Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062 (Japan)
  5. Diabetes and Endocrinology, Flinders Medical Centre, Bedford Park, SA 5042 (Australia)
  6. (Japan), E-mail: okazaki@saitama-med.ac.jp
Publication Date:
OSTI Identifier:
21043654
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 367; Journal Issue: 3; Other Information: DOI: 10.1016/j.bbrc.2007.12.188; PII: S0006-291X(08)00002-8; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; DEXTRAN; DISEASES; GENES; IN VITRO; INFLAMMATION; LIPIDS; MACROPHAGES; MICE; NITRIC OXIDE; PROSTAGLANDINS; RECEPTORS; SODIUM SULFATES

Citation Formats

Yamamoto, Keiko, Ninomiya, Yuichi, Iseki, Mioko, Nakachi, Yutaka, Kanesaki-Yatsuka, Yukiko, Yamanoue, Yu, Itoh, Toshimasa, Nishii, Yasuho, Petrovsky, Nikolai, Okazaki, Yasushi, and Division of Functional Genomics and Systems Medicine, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1241. 4-Hydroxydocosahexaenoic acid, a potent peroxisome proliferator-activated receptor {gamma} agonist alleviates the symptoms of DSS-induced colitis. United States: N. p., 2008. Web. doi:10.1016/j.bbrc.2007.12.188.
Yamamoto, Keiko, Ninomiya, Yuichi, Iseki, Mioko, Nakachi, Yutaka, Kanesaki-Yatsuka, Yukiko, Yamanoue, Yu, Itoh, Toshimasa, Nishii, Yasuho, Petrovsky, Nikolai, Okazaki, Yasushi, & Division of Functional Genomics and Systems Medicine, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1241. 4-Hydroxydocosahexaenoic acid, a potent peroxisome proliferator-activated receptor {gamma} agonist alleviates the symptoms of DSS-induced colitis. United States. doi:10.1016/j.bbrc.2007.12.188.
Yamamoto, Keiko, Ninomiya, Yuichi, Iseki, Mioko, Nakachi, Yutaka, Kanesaki-Yatsuka, Yukiko, Yamanoue, Yu, Itoh, Toshimasa, Nishii, Yasuho, Petrovsky, Nikolai, Okazaki, Yasushi, and Division of Functional Genomics and Systems Medicine, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1241. 2008. "4-Hydroxydocosahexaenoic acid, a potent peroxisome proliferator-activated receptor {gamma} agonist alleviates the symptoms of DSS-induced colitis". United States. doi:10.1016/j.bbrc.2007.12.188.
@article{osti_21043654,
title = {4-Hydroxydocosahexaenoic acid, a potent peroxisome proliferator-activated receptor {gamma} agonist alleviates the symptoms of DSS-induced colitis},
author = {Yamamoto, Keiko and Ninomiya, Yuichi and Iseki, Mioko and Nakachi, Yutaka and Kanesaki-Yatsuka, Yukiko and Yamanoue, Yu and Itoh, Toshimasa and Nishii, Yasuho and Petrovsky, Nikolai and Okazaki, Yasushi and Division of Functional Genomics and Systems Medicine, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka, Saitama 350-1241},
abstractNote = {(5E,7Z,10Z,13Z,16Z,19Z)-4-Hydroxy-5,7,10,13,16,19-docosahexaenoic acid (4-OHDHA) is a potential agonist of peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}) and antidiabetic agent as has been previously reported. As PPAR{gamma} agonists may also have anti-inflammatory functions, in this study, we investigated whether 4-OHDHA has an inhibitory effect on expression of inflammatory genes in vitro and whether 4-OHDHA could relieve the symptoms of dextran sodium sulfate (DSS)-induced colitis in a murine model of inflammatory bowel disease. 4-OHDHA inhibited production of nitric oxide and expression of a subset of inflammatory genes including inducible nitric oxide synthase (Nos2/iNOS) and interleukin 6 (Il6) by lipopolysaccharide (LPS)-activated macrophages. In addition, 4-OHDHA-treated mice when compared to control mice not receiving treatment recovered better from the weight loss caused by DSS-induced colitis. Changes in disease activity index (DAI) of 4-OHDHA-treated mice were also more favorable than for control mice and were comparable with mice treated with a typical anti-inflammatory-drug, 5-aminosalichylic acid (5-ASA). These results suggest that 4-OHDHA has potentially clinically useful anti-inflammatory effects mediated by suppression of inflammatory gene expression.},
doi = {10.1016/j.bbrc.2007.12.188},
journal = {Biochemical and Biophysical Research Communications},
number = 3,
volume = 367,
place = {United States},
year = 2008,
month = 3
}
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