Histamine suppresses epidermal keratinocyte differentiation and impairs skin barrier function in a human skin model.
Histamine suppresses epidermal keratinocyte differentiation and impairs skin barrier function in a human skin model.
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DOI：
10.1111/all.12051
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发表时间：
2013-01
期刊：
影响因子：
12.4
通讯作者：
Tschachler E
中科院分区：
文献类型：
--
作者：
Gschwandtner M;Mildner M;Mlitz V;Gruber F;Eckhart L;Werfel T;Gutzmer R;Elias PM;Tschachler E
角质形成细胞分化缺陷和皮肤屏障缺陷是特应性皮炎等炎症性皮肤病的重要特征。肥大细胞及其主要介体组胺在炎症皮肤中含量丰富，可能参与了疾病的发病机制。人原代角质形成细胞在有无组胺、组胺受体激动剂和拮抗剂的促进分化条件下培养。用实时定量聚合酶链式反应、Western印迹和免疫荧光标记技术对分化相关基因和表皮连接蛋白的表达进行定量。应用生物素作为示踪分子，对人体皮肤模型的屏障功能进行了测试。在人类角质形成细胞培养和器官型皮肤模型中加入组胺后，角蛋白1/10、微丝蛋白和氯化蛋白的表达减少了80%-95%。此外，在皮肤模型中添加组胺会导致颗粒层丢失，表皮和角质层变薄50%。组胺受体H1R激动剂2-吡啶乙胺抑制角质形成细胞分化的程度与组胺相同。相应地，H1R的拮抗剂西替利嗪几乎消除了组胺的作用。组胺可下调紧密连接蛋白occludens-1、occludin、claudin-1和claudin-4以及桥粒连接蛋白cornedesmosin和desmoglein-1的表达。示踪分子生物素很容易穿透在组胺存在下生长的皮肤培养物的紧密连接屏障，而在未经处理的对照组中，它们的扩散完全被阻止。我们的发现提示了一种新的机制，肥大细胞的激活和组胺的释放有助于炎症性皮肤病的皮肤屏障缺陷。
Defects in keratinocyte differentiation and skin barrier are important features of inflammatory skin diseases like atopic dermatitis. Mast cells and their main mediator histamine are abundant in inflamed skin and thus may contribute to disease pathogenesis. Human primary keratinocytes were cultured under differentiation-promoting conditions in the presence and absence of histamine, histamine receptor agonists and antagonists. The expression of differentiation-associated genes and epidermal junction proteins was quantified by real-time PCR, Western blot, and immunofluorescence labeling. The barrier function of human skin models was tested by the application of biotin as tracer molecule. The addition of histamine to human keratinocyte cultures and organotypic skin models reduced the expression of the differentiation-associated proteins keratin 1/10, filaggrin, and loricrin by 80–95%. Moreover, the addition of histamine to skin models resulted in the loss of the granular layer and thinning of the epidermis and stratum corneum by 50%. The histamine receptor H1R agonist, 2-pyridylethylamine, suppressed keratinocyte differentiation to the same extent as did histamine. Correspondingly, cetirizine, an antagonist of H1R, virtually abrogated the effect of histamine. The expression of tight junction proteins zona occludens-1, occludin, claudin-1, and claudin-4, as well as that of desmosomal junction proteins corneodesmosin and desmoglein-1, was down-regulated by histamine. The tracer molecule biotin readily penetrated the tight junction barrier of skin cultures grown in the presence of histamine, while their diffusion was completely blocked in nontreated controls. Our findings suggest a new mechanism by which mast cell activation and histamine release contribute to skin barrier defects in inflammatory skin diseases.
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影响因子：
14.2
作者：
De Benedetto, Anna;Rafaels, Nicholas M;McGirt, Laura Y;Ivanov, Andrei I;Georas, Steve N;Cheadle, Chris;Berger, Alan E;Zhang, Kunzhong;Vidyasagar, Sadasivan;Yoshida, Takeshi;Boguniewicz, Mark;Hata, Tissa;Schneider, Lynda C;Hanifin, Jon M;Gallo, Richard L;Novak, Natalija;Weidinger, Stephan;Beaty, Terri H;Leung, Donald Y M;Barnes, Kathleen C;Beck, Lisa A
通讯作者：
Beck, Lisa A
DOI：
10.1111/j.1468-3083.2011.04198.x
发表时间：
2012-08-01
影响因子：
9.2
作者：
Mlitz, V.;Latreille, J.;Tschachler, E.
通讯作者：
Tschachler, E.
影响因子：
6.5
作者：
Kanda, N;Watanabe, S
通讯作者：
Watanabe, S
影响因子：
6.5
作者：
Ashida, Y;Denda, M;Hirao, T
通讯作者：
Hirao, T
DOI：
10.1038/jid.2011.24
发表时间：
2011-06
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Kim BE;Howell MD;Guttman-Yassky E;Gilleaudeau PM;Cardinale IR;Boguniewicz M;Krueger JG;Leung DY
通讯作者：
Leung DY