Deficiency of n-6 polyunsaturated fatty acids is mainly responsible for atopic dermatitis-like pruritic skin inflammation in special diet-fed hairless mice
Deficiency of n-6 polyunsaturated fatty acids is mainly responsible for atopic dermatitis-like pruritic skin inflammation in special diet-fed hairless mice
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DOI：
10.1111/exd.12120
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发表时间：
2013-04-01
影响因子：
3.6
通讯作者：
Nabe, Takeshi
中科院分区：
文献类型：
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作者：
Fujii, Masanori;Nakashima, Hiroyuki;Nabe, Takeshi
喂食特殊饮食HR-AD的无毛小鼠发生特应性皮炎（AD）样皮肤炎症，伴有皮肤屏障缺陷和瘙痒相关的抓挠;然而，引起皮炎的成分仍不清楚。在这项研究中，我们研究了某些多不饱和脂肪酸（PUFAs）的缺乏是否参与HR-AD诱导的AD。通过饮食补充或灌胃给予HR-AD喂养的小鼠高纯度PUFA。用气相色谱-质谱法测定血清和皮肤中的脂肪酸水平。在HR-AD喂养小鼠的血清中，亚油酸（LA，18：2n-6）和α-亚麻酸（ALA，18：3 n-3）及其代谢产物显著降低。当给小鼠喂食补充有LA或ALA的HR-AD时，补充LA而不是ALA可以完全预防AD样症状的发生。相对高剂量的ALA轻微减轻皮肤屏障缺陷，但不瘙痒相关的抓挠或皮肤炎症。另一方面，灌胃给予LA代谢物，如c-亚麻酸和花生四烯酸（AA），显着改善建立皮炎，而不增加血清和皮肤中的LA。此外，AA诱导的皮炎改善不受5-脂氧合酶（5-LOX）和环氧合酶（考克斯）的药理学阻断的影响，表明5-LOX或COX介导的AA代谢产物不参与改善。总之，我们的研究结果表明，缺乏n-6 PUFAs是主要负责AD样症状的HR-AD喂养。因此，该模型可用于研究AD中与n-6 PUFA缺乏相关的病理机制。
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 alpha-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 c-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.