title: Deficiency of n-6 polyunsaturated fatty acids is mainly responsible for atopic dermatitis-like pruritic skin inflammation in special diet-fed hairless mice.
abstract: Hairless mice fed a special diet, HR-AD, develop atopic dermatitis (AD)-like skin inflammation with skin barrier defects and itch-related scratching; however, the ingredient(s) causing the dermatitis remains unclear. In this study, we examined whether deficiency of certain polyunsaturated fatty acids (PUFAs) is involved in HR-AD-induced AD. High-purity PUFAs were given to HR-AD-fed mice by dietary supplementation or gavage. Fatty acid levels in the serum and skin were determined by using gas chromatography-mass spectrometry. In serum from HR-AD-fed mice, linoleic acid (LA, 18:2n-6) and α-linolenic acid (ALA, 18:3n-3), as well as their metabolites, were markedly decreased. When mice were fed HR-AD supplemented with LA or ALA in an amount equal to that contained in a normal diet, the development of AD-like symptoms was completely prevented by supplementation with LA but not with ALA. Relatively high dose of ALA slightly alleviated skin barrier defects, but did neither itch-related scratching nor skin inflammation. On the other hand, gavage administration of LA metabolites, such as γ-linolenic acid and arachidonic acid (AA), significantly ameliorated established dermatitis without increasing LA in the serum and skin. Moreover, AA-induced amelioration of dermatitis was not affected by pharmacological blockade of 5-lipoxygenase (5-LOX) and cyclooxygenase (COX), suggesting no involvement of 5-LOX- or COX-mediated AA metabolites in the amelioration. In conclusion, our results indicate that deficiency of n-6 PUFAs is mainly responsible for AD-like symptoms by HR-AD feeding. Thus, this model could be useful for studying the pathomechanisms associated with deficiency of n-6 PUFAs in AD.
authors.affiliation: Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto, Japan. fujii@mb.kyoto-phu.ac.jp
authors.forename: Masanori
authors.initials: M
authors.lastname: Fujii
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakashima
authors.forename: Junko
authors.initials: J
authors.lastname: Tomozawa
authors.forename: Yuki
authors.initials: Y
authors.lastname: Shimazaki
authors.forename: Chie
authors.initials: C
authors.lastname: Ohyanagi
authors.forename: Naomi
authors.initials: N
authors.lastname: Kawaguchi
authors.forename: Susumu
authors.initials: S
authors.lastname: Ohya
authors.forename: Shigekatsu
authors.initials: S
authors.lastname: Kohno
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nabe
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000008:administration & dosage; D003876:Dermatitis, Atopic / Q000178:diet therapy / Q000209:etiology* / Q000378:metabolism; D004032:Diet / Q000009:adverse effects; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000378:metabolism; D043371:Fatty Acids, Omega-6 / Q000097:blood / Q000172:deficiency* / Q000378:metabolism; D005260:Female; D019787:Linoleic Acid / Q000008:administration & dosage / Q000378:metabolism; D051379:Mice; D008812:Mice, Hairless; D011537:Pruritus / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000378:metabolism / Q000473:pathology
chemical_list: D004042:Dietary Fats, Unsaturated; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D016718:Arachidonic Acid; D019787:Linoleic Acid