Dry skin/barrier dysfunction is considered to be one of the characteristic features of atopic dermatitis (AD). When HR-1 hairless mice are fed a special diet, HR-AD, dry red skin is induced. We examined whether HR-AD-fed mouse could be used as a model for AD by showing itch-associated scratching behaviour and by analysing the immunological change. HR-1 mice were fed HR-AD from 4 weeks old. HR-AD-fed mice showed severe dry skin symptoms accompanied by a decrease in dermal water content and an increase in transepidermal water loss and prolonged scratching bout duration on day 14 or 28. These symptoms became gradually worse until day 56. Marked epidermal hyperplasia and slight increase in CD4+ cells in the skin were observed from day 28. In contrast, increases in circulating T cells and serum immunoglobulin E were seen from day 41. Other skin-infiltrating inflammatory cells, such as eosinophils and mast cells, were increased on day 56 but not on day 28. Though daily oral treatment with dexamethasone reduced the increased numbers of these cells, it did not affect the dry skin symptoms or the prolonged scratching episodes. In contrast, the development of dry skin was inhibited by feeding with 10% normal diet-containing HR-AD. The skin barrier dysfunction in HR-AD-fed mice is closely associated with the development of AD-like pruritus. Changes in the immunological parameters observed may be the consequence of skin barrier dysfunction. Our findings suggest that HR-AD-fed mouse could be used as a dry skin-based experimental model for AD.

No 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.

No abstract

3-month-old mice (Fig. 2a). Intriguingly, the tip did express increased amounts of the antioxidants Ucp2, Gpx1 and Sod1 compared to the other regions. As the amount of sebocytes was controlled for by the use of Fabp4, the increased antioxidant expression in the tip may be due to differences within the hair cycle or for protection from external damage and renders further investigation. Despite this, the lack of a difference in the thermogenic UCP1 protein and RNA within the regions indicates that UCP1 within the sebocyte population is irresponsive to regional temperature variations in the tail.Lastly, because the amount of BAT and UCP1 activity is greatly reduced or even lost during ageing (5) and this same ageing pattern could be recapitulated in tail, Ucp1 expression and protein localization were compared in tails among young (3 months old) and aged (12 months old) mice. Age had no effect on the expression of the well-characterized thermogenic genes Ucp1 or Prdm16 between mice ( Figure S3a). In addition, neither the immunofluorescence intensity nor the location of UCP1 protein differed notably in the terminal tail region between young and aged mice ( Figure S3b). ConclusionsWe extended the results by Mori et al. (6) showing that Ucp1 is expressed in various locations in the tail sebaceous glands. Our data, however, do not indicate that the role of sebaceous gland UCP1 is one of thermoregulation. Further, we provide evidence that UCPs in the sebaceous gland serve an alternative antioxidant role as described in other organs (8).