Anti-inflammatory Lipid Mediators Derived from ω-6 and ω-3 Polyunsaturated Fatty Acids as a Treatment Option for IBD

Shin      Nishiumi; Izumi      Kure; Tsukasa      Ishida; Makoto      Ooi; Tomoo      Yoshie; Hiromu      Kutsumi; Takeshi      Azuma; Masaru      Yoshida

Abstract

Lipoxins and resolvins are endogenous lipid mediators derived from ω-6 and ω-3 polyunsaturated fatty acids (PUFAs), respectively. Lipoxins, such as lipoxin A4 (LXA4) and lipoxin B4 (LXB4), are known as the first proresolving mediators, and their appearance leads to the resolution of inflammation. In addition, resolvins, such as D series resolvins (RvD) and E series resolvins (RvE), play important roles in the resolution of inflammation. So far, the anti-inflammatory effects of lipoxins and resolvins have been revealed in various experimental models of inflammatory disorders, and much attention has been paid to PUFAs and lipid mediators derived from PUFAs as a therapeutic strategy for inflammatory disorders including inflammatory bowl diseases (IBD). Recent studies using animal experimental models demonstrated that lipoxins; aspirin-triggered lipoxins; and their stable analogues, such as LXA4 and aspirin-triggered 15-epi-LXA4, were able to attenuate colitis. Resolvins, such as RvE1, were also demonstrated to protect against colitis. Moreover, it has been proposed that the biological abilities of endogenous anti-inflammatory lipid mediators are induced via their corresponding receptors, for example, FPR2/ALX for LXA4 and ChemR23 for RvE1, and the expression levels of their receptors were reported to be increased in macrophages and intestinal epithelium stimulated with exogenous antigens such as lipopolysaccaride. In this paper, the anti-inflammatory effects of lipid mediators derived from PUFAs, especially LXA4 and RvE1, are outlined, and the possibility of their use as a therapeutic strategy for IBD is discussed.

Keywords: Lipoxin, LXA4, Resolvin, RvE1, Anti-inflammation, Inflammatory bowl disease, Dextran sulfate sodium (DSS), phylogenetically, hamster, Flare-up