Cellular Physiology and Biochemistry Cellular Physiology and Biochemistry Expression of Nodal on Bronchial Epithelial Cells Influenced by Lung Microbes through Dna Methylation Modulates the Differentiation of T-helper Cells
Cellular Physiology and Biochemistry Cellular Physiology and Biochemistry Expression of Nodal on Bronchial Epithelial Cells Influenced by Lung Microbes through Dna Methylation Modulates the Differentiation of T-helper Cells
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通讯作者：
Shui-Yu Liu;Yurong Tan;Lili Wang;Guojun Wu;X. Qin;Qiongshan Ma;Y. Zhou
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作者：
Shui-Yu Liu;Yurong Tan;Lili Wang;Guojun Wu;X. Qin;Qiongshan Ma;Y. Zhou
这是一篇开放获取文章，根据知识共享归因-非商业性3.0未移植许可（CC BY-NC）（www.karger.com/OA-license）的条款进行许可，仅适用于该文章的在线版本。仅允许用于非商业目的的分发。摘要背景/目的：本实验室前期的研究表明，支气管上皮细胞（BECs）上的Nodal分子受到各种肺部微生物的调节。本研究旨在确定Nodal对BECs增殖和BECs诱导的Th细胞分化的影响。还鉴定了不同肺微生物处理后Nodal表达的表观遗传机制。方法：采用实时荧光定量PCR（Real-time polymerization chain reaction，PCR）和western blot方法检测Nodal基因的表达。流式细胞仪检测BECs增殖及诱导Th细胞分化的作用。还通过飞行时间质谱分析了Nodal启动子中CpG岛的甲基化水平。结果：Nodal可促进BECs增殖，并诱导BECs诱导Th细胞由Th 1向Th 2和Th 17分化。Nodal基因启动子在正常BEC中呈高甲基化状态。铜绿假单胞菌和鲍曼不动杆菌通过甲基化修饰抑制Nodal基因的表达，而RSV则通过甲基化修饰促进Nodal基因的表达。结论：提示Nodal促进Th 2和Th 17分化，抑制Th 1分化，可能导致气道微环境失衡。铜绿假单胞菌或鲍曼不动杆菌可能通过启动子区DNA甲基化修饰抑制Nodal基因的表达，从而有望用于治疗气道高反应性。
This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only. Abstract Background/Aims: The previous study in our lab showed that Nodal molecule on bronchial epithelial cells (BECs) was modulated by all kinds of lung microbes. The present study was designed to determine the effects of Nodal on proliferation of BECs and BECs-induced differentiation of T-helper (Th) cells. The epigenetic mechanisms of Nodal expression following treatments of different lung microbes were also identified. Methods: Real-time polymerization chain reaction (PCR) and western blot were used to determine the expression of Nodal. Flow cytometry was used to observe the effects of proliferation of BECs and subsequent BECs-induced differentiation of Th cells. Methylation levels of CpG islands in Nodal promoters were also analyzed by time of flight mass spectrometry. Results: The results showed that Nodal promoted proliferation of BECs and BECs-induced differentiation of Th cell from Th1 to Th2 and Th17. Nodal promoter showed a hyper-methylation in normal BECs. Through methylation modification in the promoter, P. aeruginosa or A.baumanni inhibited the expression of Nodal while RSV promoted the expression of Nodal. Conclusions: Our data showed that Nodal promoted Th2 and Th17 differentiation and inhibited Th1 differentiation which may cause imbalance of airway microenvironment. P. aeruginosa or A.baumanni may be hopeful for the treatment of airway hyperresponsveness by inhibition Nodal expression through DNA methylation modification in the promoter.