Inflammatory cytokine-mediated induction of serine racemase in atopic dermatitis.

Inflammatory cytokine-mediated induction of serine racemase in atopic dermatitis.
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DOI:
10.1111/jcmm.13592
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发表时间:
2018-06
影响因子:
5.3
通讯作者:
Shimizu T
Shimizu T
中科院分区:
医学2区
文献类型:
--
作者:
Yoshihisa Y;Rehman MU;Nakagawa M;Matsukuma S;Makino T;Mori H;Shimizu T

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丝氨酸消旋酶(SR)是一种催化d -丝氨酸合成的酶,d -丝氨酸是中枢神经系统N -甲基- d -天冬氨酸(NMDA)型谷氨酸受体的内源性凝聚剂。我们之前的研究表明,SR在野生型(WT)小鼠的表皮中表达,而在SR敲除(KO)小鼠中不表达。此外,SR免疫反应性仅在WT小鼠表皮的颗粒层和锥形层中发现。这些结果表明,SR参与表皮角质形成细胞的分化和皮肤屏障的形成。然而,其在皮肤屏障功能障碍,如特应性皮炎(AD)中的作用仍然难以捉摸。AD是一种慢性皮肤炎症性疾病,据报道,AD的临床表现偶尔与心理因素有关。因此,本研究使用胶带剥离法检测了AD患者和健康对照者角质层中d -丝氨酸的含量。皮肤样本取自AD患者病变组和健康人的脸颊和上臂皮肤。与健康个体相比,AD受累皮肤的d -丝氨酸含量显著增加。免疫组织化学分析也显示AD患者表皮中SR表达增加。此外,肿瘤坏死因子- α或巨噬细胞迁移抑制因子刺激可显著提高体外培养的人角质形成细胞中SR的表达。综上所述,这些发现表明d -丝氨酸在AD病变皮肤中的表达特别强烈,而角化细胞中的SR表达与炎症细胞因子有关。
Serine racemase (SR) is an enzyme that catalyses the synthesis of d‐serine, an endogenous coagonist for N‐methyl‐D‐aspartate (NMDA)‐type glutamate receptor in the central nervous system. Our previous study demonstrated that SR was expressed in the epidermis of wild‐type (WT) mice but not in SR knockout (KO) mice. In addition, SR immune‐reactivity was only found in the granular and cornified layers of the epidermis in WT mice. These findings suggested that SR is involved in the differentiation of epidermal keratinocytes and the formation of the skin barrier. However, its role in skin barrier dysfunction such as atopic dermatitis (AD) remains elusive. AD is a chronic inflammatory disease of skin, and the clinical presentation of AD has been reported to be occasionally associated with psychological factors. Therefore, this study examined the content of d‐serine in stratum corneum in AD patients and healthy controls using a tape‐stripping method. Skin samples were collected from the cheek and upper arm skin of AD patient's lesion and healthy individuals. The d‐serine content was significantly increased in the involved skin of AD in comparison with healthy individuals. An immunohistochemical analysis also revealed an increased SR expression in the epidermis of AD patients. Furthermore, the SR expression in cultured human keratinocytes was significantly increased by the stimulation with tumour necrosis factor ‐α or macrophage migration inhibitory factor. Taken together, these findings suggest that d‐serine expressed particularly strongly in AD lesional skin and that the SR expression in the keratinocytes is linked to inflammatory cytokines.
DOI: 10.1038/jid.2014.22
发表时间: 2014-06
影响因子: 6.5
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