ヘアレスマウスにおける食餌誘発アトピー性皮膚炎の発症要因の解明

• 藤井 正徳

  京都薬科大学病態薬科学系薬理学分野

書誌事項

タイトル別名

• Pathogenesis of Diet-induced Atopic Dermatitis in Hairless Mice
• ヘアレスマウス ニ オケル ショクジ ユウハツ アトピーセイ ヒフエン ノ ハッショウ ヨウイン ノ カイメイ

抄録

 Atopic dermatitis (AD) is a common pruritic chronic skin disease. AD pathogenesis remains elusive, but may involve complex interplays among skin barrier dysfunction, Th2 inflammation, and pruritus. Current treatments for AD are still limited to symptomatic therapies. We previously showed that HR-1 hairless mice fed a special diet (HR-AD) develop AD-like symptoms; however, the ingredient(s) causing dermatitis remain unclear. In this study, we examined whether the deficiency of certain polyunsaturated fatty acids (PUFAs) was involved in the diet-induced AD pathogenesis. In the serum of HR-AD-fed mice, levels of linoleic acid (LA, 18:2n-6) and α-linolenic acid (ALA, 18:3n-3), as well as their metabolites, were markedly decreased. HR-AD-induced AD symptoms were significantly ameliorated by LA supplementation, and to a lesser extent by ALA supplementation. In addition, LA metabolites, such as γ-linolenic acid and arachidonic acid, had effects similar to those of LA. Further, using semi-purified custom diets, we attempted to reproduce HR-AD-induced AD symptoms. Unexpectedly, a deficiency in unsaturated fatty acids (UFAs) alone caused mild symptoms. However, several modifications of fat and carbohydrate components in the diet revealed that dietary deficiencies of UFA and cornstarch were required to fully induce severe AD symptoms. Furthermore, we examined the influence of genetic background on the development of diet-induced AD and found that a hypomorphic mutation in the hairless gene Hr, encoding a nuclear receptor (NR) corepressor, was essential for the complete development of diet-induced pruritic atopic skin. Thus, our findings suggest that certain PUFAs and NRs are new, potential therapeutic targets for treating AD.<br>

収録刊行物

• 薬学雑誌

  薬学雑誌 137 (1), 49-54, 2017-01-01

  公益社団法人 日本薬学会

キーワード

• atopic dermatitis
• polyunsaturated fatty acid
• corn starch
• hairless gene
• animal model

詳細情報

• CRID: 1390001206126473856
• NII論文ID: 130005180844
• NII書誌ID: AN00284903
• DOI: 10.1248/yakushi.16-00200
• ISSN: 13475231
• ISSN: 00316903
• NDL書誌ID: 027836751
• PubMed: 28049895
• Web Site: http://id.ndl.go.jp/bib/027836751
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I027836751
• Web Site: https://www.jstage.jst.go.jp/article/yakushi/137/1/137_16-00200/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2017254556
• 本文言語コード: ja
• データソース種別:
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  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
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