کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8716245 | 1587880 | 2018 | 37 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Epidermal Overexpression of Xenobiotic Receptor PXR Impairs the Epidermal Barrier and Triggers Th2 Immune Response
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کلمات کلیدی
ILCTEWLPXRCYP450T helperTSLPK14Transepidermal water loss - از دست دادن آب دریچهAtopic dermatitis - درماتیت آتوپیکDendritic cell - سلول دندریتیکinnate lymphoid cell - سلول لنفاوی ذاتیtype 2 innate lymphoid cells - سلول های لنفاوی ذاتی نوع 2Cytochrome P450 - سیتوکروم پی۴۵۰keratin 14 - کراتین 14Pregnane X receptor - گیرنده پیش گران X
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
امراض پوستی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The skin is in daily contact with environmental pollutants, but the long-term effects of such exposure remain underinvestigated. Many of these toxins bind and activate the pregnane X receptor (PXR), a ligand-activated transcription factor that regulates genes central to xenobiotic metabolism. The objective of this work was to investigate the effect of constitutive activation of PXR in the basal layer of the skin to mimic repeated skin exposure to noxious molecules. We designed a transgenic mouse model that overexpresses the human PXR gene linked to the herpes simplex VP16 domain under the control of the keratin 14 promoter. We show that transgenic mice display increased transepidermal water loss and elevated skin pH, abnormal stratum corneum lipids, focal epidermal hyperplasia, activated keratinocytes expressing more thymic stromal lymphopoietin, a T helper type 2/T helper type 17 skin immune response, and increased serum IgE. Furthermore, the cutaneous barrier dysfunction precedes development of the T helper type 2/T helper type 17 inflammation in transgenic mice, thereby mirroring the time course of atopic dermatitis development in humans. Moreover, further experiments suggest increased PXR signaling in the skin of patients with atopic dermatitis when compared with healthy skin. Thus, PXR activation by environmental pollutants may compromise epidermal barrier function and favor an immune response resembling atopic dermatitis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Investigative Dermatology - Volume 138, Issue 1, January 2018, Pages 109-120
Journal: Journal of Investigative Dermatology - Volume 138, Issue 1, January 2018, Pages 109-120
نویسندگان
Andreas Elentner, Matthias Schmuth, Nikolaos Yannoutsos, Thomas O. Eichmann, Robert Gruber, Franz P.W. Radner, Martin Hermann, Barbara Del Frari, Sandrine Dubrac,