背景:特应性皮炎(AD)是一种慢性复发性皮肤病,具有瘙痒性皮肤症状。我们先前报道了二高-γ-亚麻酸(DGLA)在NC/Tnd小鼠中预防AD的发展,尽管机制尚不清楚。
目的:我们试图研究DGLA对NC/Tnd小鼠AD发展的预防作用机制。
方法:给予含有DGLA的饮食的NC/Tnd小鼠的临床结果,花生四烯酸,或二十碳五烯酸进行比较。还对各组皮肤中的脂质介质含量进行了定量。此外,测量了用DGLA或前列腺素D1(PGD1)处理的RBL-2H3肥大细胞中脂质介质的释放。此外,测定了PGD1对PAM212角质形成细胞胸腺基质淋巴细胞生成素(TSLP)基因表达的影响。
结果:只有含DGLA的饮食能抑制体内皮炎的发展。通过量化皮肤中20碳脂肪酸衍生的类二十烷酸,发现DGLA的应用上调PGD1,这与NC/Tnd小鼠的更好结果相关。此外,我们证实,肥大细胞在DGLA暴露后产生PGD1,从而对免疫球蛋白E介导的脱颗粒产生抑制作用。PGD1还抑制角质形成细胞中TSLP的基因表达。
结论:这些结果表明,口服DGLA通过调节PGD1的供应对NC/Tnd小鼠的AD发展产生预防作用。
BACKGROUND: Atopic dermatitis (AD) is a chronic and relapsing skin disorder with pruritic skin symptoms. We previously reported that dihomo-γ-linolenic acid (DGLA) prevented the development of AD in NC/Tnd mice, though the mechanism remained unclear.
OBJECTIVE: We attempted to investigate the mechanism of preventive effect of DGLA on AD development in NC/Tnd mice.
METHODS: The clinical outcomes of NC/Tnd mice that were given diets containing DGLA, arachidonic acid, or eicosapentaenoic acid were compared. Lipid mediator contents in the skin in each group were also quantified. In addition, release of lipid mediators from RBL-2H3 mast cells treated with either DGLA or prostaglandin D1 (PGD1) was measured. Furthermore, effect of PGD1 on gene expression of thymic stromal lymphopoietin (TSLP) in PAM212 keratinocyte cells was determined.
RESULTS: Only DGLA containing diet suppressed the development of dermatitis in vivo. By quantifying the 20-carbon fatty acid-derived eicosanoids in the skin, the application of DGLA was found to upregulate PGD1, which correlated with a better outcome in NC/Tnd mice. Moreover, we confirmed that mast cells produced PGD1 after DGLA exposure, thereby exerting a suppressive effect on immunoglobulin E-mediated degranulation. PGD1 also suppressed gene expression of TSLP in keratinocytes.
CONCLUSIONS: These results suggest that oral administration of DGLA causes preventive effects on AD development in NC/Tnd mice by regulating the PGD1 supply.