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 ( PPARgamma) and antidiabetic agent as has been previously reported. As PPARgamma 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.
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Authors | Keiko Yamamoto, Yuichi Ninomiya, Mioko Iseki, Yutaka Nakachi, Yukiko Kanesaki-Yatsuka, Yu Yamanoue, Toshimasa Itoh, Yasuho Nishii, Nikolai Petrovsky, Yasushi Okazaki |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 367
Issue 3
Pg. 566-72
(Mar 14 2008)
ISSN: 1090-2104 [Electronic] United States |
PMID | 18191038
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 4-hydroxy-5,7,10,13,16,19-docosahexaenoic acid
- Anti-Inflammatory Agents
- Fatty Acids, Unsaturated
- Lipopolysaccharides
- PPAR gamma
- RNA, Messenger
- Nitric Oxide
- Dextran Sulfate
- Nitric Oxide Synthase Type II
- Nos2 protein, mouse
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Topics |
- Animals
- Anti-Inflammatory Agents
(therapeutic use)
- Body Weight
(drug effects)
- Cell Line
- Colitis
(chemically induced, drug therapy)
- Dextran Sulfate
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Fatty Acids, Unsaturated
(therapeutic use)
- Gene Expression
(drug effects)
- Gene Transfer Techniques
- Lipopolysaccharides
(pharmacology)
- Macrophage Activation
(drug effects)
- Male
- Mice
- Mice, Inbred C57BL
- Nitric Oxide
(metabolism)
- Nitric Oxide Synthase Type II
(genetics)
- PPAR gamma
(agonists)
- Promoter Regions, Genetic
(drug effects)
- RNA, Messenger
(metabolism)
- Severity of Illness Index
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