4-Hydroxydocosahexaenoic acid, a potent peroxisome proliferator-activated receptor γ agonist alleviates the symptoms of DSS-induced colitis

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• 作者：Keiko Yamamoto ; Yuichi Ninomiya ; Mioko Iseki ; Yutaka Nakachi ; Yukiko Kanesaki-Yatsuka ; Yu Yamanoue ; Toshimasa Itoh ; Yasuho Nishii ; Nikolai Petrovsky ; Yasushi Okazaki
• 关键词：Docosahexaenoic acid ; Peroxisome proliferator-activated receptor-γ ; Anti-inflammatory effect ; 15-Deoxy-Δ ; ¹² ; 14-prostaglandin J₂ ; Inflammatory bowel disease ; Lipopolysaccharide ; Lipid mediators
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2008
• 出版时间：14 March 2008
• 年：2008
• 卷：367
• 期：3
• 页码：566-572
• 全文大小：293 K

文摘

(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-γ (PPARγ) and antidiabetic agent as has been previously reported. As PPARγ 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.