2,3,7,8-Tetrachlorodibenzo-p-dioxin alters the differentiation pattern of human keratinocytes in organotypic culture
2,3,7,8-Tetrachlorodibenzo-p-dioxin alters the differentiation pattern of human keratinocytes in organotypic culture
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DOI：
10.1006/taap.2001.9202
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发表时间：
2001-09-01
影响因子：
3.8
通讯作者：
Allen-Hoffmann, BL
中科院分区：
文献类型：
--
作者：
Loertscher, JA;Sattler, CA;Allen-Hoffmann, BL
人类暴露于环境毒素2,3,7,8-四氯二苯并-对二恶英（TCDD）产生严重的皮肤病理称为氯痤疮。在这些研究中，我们采用三维，器官型模型系统来研究TCDD对人体皮肤的影响。该模型使用了自发永生化的人角质细胞系NIKS，并概括了在完整的人皮肤中发现的三维微环境和上皮-间充质相互作用。用TCDD处理器官型培养引起角化细胞终末分化模式的改变。光镜和电镜分析显示，与二甲基亚砜处理的对照组相比，tcdd处理的器官型培养物在更早的时间点上有完全分化的角质层。此外，tcdd处理的器官型培养物表现出几种分化特异性蛋白标记物的异常分布。通过对5-溴-2 ' -脱氧尿苷（BrdU）阳性细胞核的定量测量，TCDD和dmso处理的器官型培养的基底细胞在增殖方面没有差异。基底层外未检测到异常的BrdU摄取。TUNEL标记和活性caspase-3抗体的免疫组织化学染色均未显示，与对照组相比，tcdd处理的器官型培养细胞凋亡增加。这些数据清楚地表明，TCDD调节人分层上皮模型中的稳态，而不依赖于增殖和凋亡的变化，仅通过影响角化细胞终末分化。tcdd对分化特异性蛋白的影响导致了组织结构的深刻变化。(C) 2001学术出版社。
Human exposure to the environmental toxin 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces a severe skin pathology known as chloracne. In these studies we employed a three-dimensional, organotypic model system to study the effects of TCDD on human skin. This model uses the spontaneously immortalized human keratinocyte cell line NIKS and recapitulates both the three-dimensional microenvironment and epithelial-mesenchymal interactions found in intact human skin. Treatment of the organotypic cultures with TCDD causes alterations in the pattern of keratinocyte terminal differentiation. Analysis at both the light and electron microscope levels reveals a fully differentiated cornified layer in TCDD-treated organotypic cultures at earlier time points than observed in vehicle (dimethyl sulfoxide)-treated controls. Furthermore, TCDD-treated organotypic cultures exhibit aberrant distribution of several differentiation-specific protein markers. Basal cells in TCDD- and DMSO-treated organotypic cultures show no differences in proliferation as measured by quantification of 5-bromo-2 ' -deoxyuridine (BrdU)-positive nuclei. No aberrant BrdU uptake was detected outside of the basal layer. Neither TUNEL labeling nor immunohistochemical staining with an antibody to active caspase-3 revealed increased apoptosis in TCDD-treated organotypic cultures relative to controls. These data clearly indicate that TCDD modulates homeostasis in a model of human stratifying epithelium independent of changes in proliferation and apoptosis, exclusively by impacting keratinocyte terminal differentiation. This TCDD-induced effect on differentiation-specific proteins results in profound changes in the tissue architecture. (C) 2001 Academic Press.