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: Tsukasa Ishida, Shin Nishiumi, Toshihito Tanahashi, Akifumi Yamasaki, Asahi Yamazaki, Takahiro Akashi, Ikuya Miki, Yasuyuki Kondo, Jun Inoue, Shoji Kawauchi, Takeshi Azuma, Masaru Yoshida, Shigeto Mizuno
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 699 Issue 1-3 Pg. 6-13 (Jan 15 2013) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 23201070 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Inflammation Mediators
• Linoleic Acids
• Lipopolysaccharides
• NF-kappa B
• Polyunsaturated Alkamides
• linoleoyl ethanolamide
• Glycyrrhizic Acid
• Dinitrofluorobenzene

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Cell Line
• Cytokines (metabolism)
• Dermatitis, Contact (drug therapy, pathology)
• Dinitrofluorobenzene (toxicity)
• Disease Models, Animal
• Female
• Glycyrrhizic Acid (pharmacology)
• Inflammation (drug therapy, pathology)
• Inflammation Mediators (metabolism)
• Linoleic Acids (pharmacology)
• Lipopolysaccharides (toxicity)
• Macrophages (drug effects, pathology)
• Mice
• Mice, Inbred BALB C
• NF-kappa B (metabolism)
• Polyunsaturated Alkamides (pharmacology)
• Signal Transduction (drug effects)