title: Linoleoyl ethanolamide reduces lipopolysaccharide-induced inflammation in macrophages and ameliorates 2,4-dinitrofluorobenzene-induced contact dermatitis in mice.
abstract: In our previous study, it was found that linoleoyl ethanolamide (LE) is present in sake lees, which are produced as a byproduct during the making of Japanese sake. LE is a fatty acid ethanolamide, which have been demonstrated to exert a variety of biological functions, and in this study, the anti-inflammatory effects of LE were examined using in vitro cell culture and in vivo animal experiments. In mouse RAW264.7 macrophages, LE suppressed the lipopolysaccharide (LPS)-induced expression of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6. In addition, LE inhibited LPS-induced increases in the levels of cyclooxygenase enzyme-2 and prostaglandin E(2), which are indicators of inflammation. The inhibitory effect of LE on the release of TNF-α was stronger than that of dipotassium glycyrrhizinate, which is widely used in external human skin care treatments. LE also suppressed the LPS-induced activation of Toll-like receptor 4 signaling and nuclear translocation of nuclear factor-κB (NF-κB) p65. In a contact dermatitis animal model, applying LE to affected ear skin ameliorated 2,4-dinitrofluorobenzene-induced contact dermatitis and pro-inflammatory cytokine expression at inflamed sites. These results indicate that LE exerts anti-inflammatory effects by inhibiting NF-κB signaling, and LE is proposed to be a useful therapeutic agent against contact dermatitis.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Ishida
authors.forename: Shin
authors.initials: S
authors.lastname: Nishiumi
authors.forename: Toshihito
authors.initials: T
authors.lastname: Tanahashi
authors.forename: Akifumi
authors.initials: A
authors.lastname: Yamasaki
authors.forename: Asahi
authors.initials: A
authors.lastname: Yamazaki
authors.forename: Takahiro
authors.initials: T
authors.lastname: Akashi
authors.forename: Ikuya
authors.initials: I
authors.lastname: Miki
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kondo
authors.forename: Jun
authors.initials: J
authors.lastname: Inoue
authors.forename: Shoji
authors.initials: S
authors.lastname: Kawauchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Azuma
authors.forename: Masaru
authors.initials: M
authors.lastname: Yoshida
authors.forename: Shigeto
authors.initials: S
authors.lastname: Mizuno
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D003877:Dermatitis, Contact / Q000188:drug therapy* / Q000473:pathology; D004139:Dinitrofluorobenzene / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D019695:Glycyrrhizic Acid / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008041:Linoleic Acids / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D008041:Linoleic Acids; D008070:Lipopolysaccharides; D016328:NF-kappa B; D053284:Polyunsaturated Alkamides; C109347:linoleoyl ethanolamide; D019695:Glycyrrhizic Acid; D004139:Dinitrofluorobenzene