权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

ANALYSIS OF MECHANISMS OF DECREASED CERAMIDE PRODUCTION IN CORNEUM STRATUM PATIENTS WITH ATOPIC DERMATITIS

特应性皮炎患者角质层神经酰胺生成减少的机制分析

基本信息

批准号：
11470168
负责人：
MORIKAWA Akihiro
金额：
$ 1.73万
依托单位：
GUNMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

1) Impaired barrier function may contribute to the pathophysiology of atopic dermatitis. Ceramides are the main polar lipids of the stratum corneum and play an important role in skin barrier function, cell adhesion and epidermal differentiation. The transepidermal water loss (TEWL), serum IgE and eosinophils count in the peripheral blood were measured in children with atopic dermatitis. The level of TEWL was significantly higher in children with atopic dermatitis than those with bronchial asthma or controls. Neither the level of serum IgE nor eosinophils count were associated with the level of TEWL, suggesting that impaired barrier function is independent of atopic predisposition.2) To elucidate the mechanisms that are involved in the decrease of ceramide levels in atopic dry ski, we evaluated the possible role of the gene for sphingomyelinase, which is a major enzyme of ceramide production, in modulating atopic dermatitis in the Japanese population. We screened all 6 exons of the sphingomyelinase gene from 5 subjects for mutations by direct polymerase chain reaction (PCR) sequencing. The sphingomyelinase gene polymorphisms were genotyped by PCR fragment length polymorphism analysis. We also evaluated the gene polymorphism for the IL-4 receptor Q576R and STAT6, which is a key transcription factor involved in both IL-4 and IL-13-mediated biological responses. We found a novel dinucleotide repeat polymorphism in the first exon of the sphingomyelinase gene. The genotypes were classified into 6 groups according to the number of hexamer repeats present, from 5 to 11. The frequency of the 7 repeat homozygote was higher in children with atopic dermatitis than controls. This repeat polymorphism was not associated with the polymorphism in the IL-4 receptor (Q576R) and stat6. This suggests that genetic variation in the sphingomyelinase may be associated with predisposition to atopic dermatitis. In addition, this polymorphism may be independent of atopic gene.

1)屏障功能受损可能与特应性皮炎的病理生理有关。神经酰胺是角质层的主要极性脂质，在皮肤屏障功能、细胞粘附和表皮分化中起重要作用。测定特应性皮炎患儿经皮失水（TEWL）、血清IgE及外周血嗜酸性粒细胞计数。特应性皮炎患儿TEWL水平明显高于支气管哮喘患儿或对照组。血清IgE水平和嗜酸性粒细胞计数均与TEWL水平无关，提示屏障功能受损与特应性易感性无关。2)为了阐明特应性干滑雪中神经酰胺水平降低的机制，我们评估了鞘磷脂酶基因在调节日本人群特应性皮炎中的可能作用，鞘磷脂酶是神经酰胺生产的主要酶。我们通过直接聚合酶链反应（PCR）测序，从5名受试者中筛选鞘磷脂酶基因的全部6个外显子进行突变。利用PCR片段长度多态性分析对鞘磷脂酶基因多态性进行基因分型。我们还评估了IL-4受体Q576R和STAT6的基因多态性，STAT6是参与IL-4和il -13介导的生物反应的关键转录因子。我们在鞘磷脂酶基因的第一外显子上发现了一个新的二核苷酸重复多态性。根据存在的六聚体重复数将基因型分为6组，从5到11。特应性皮炎患儿7重复纯合子的频率高于对照组。这种重复多态性与IL-4受体（Q576R）和stat6的多态性无关。这表明鞘磷脂酶的遗传变异可能与特应性皮炎的易感性有关。此外，这种多态性可能与特应性基因无关。