DNAJA4 deficiency enhances NF-kappa B-related growth arrest induced by hyperthermia in human keratinocytes.
DNAJA4 deficiency enhances NF-kappa B-related growth arrest induced by hyperthermia in human keratinocytes.
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DNAJA4 缺陷会增强人角质形成细胞中高温诱导的 NF-κ B 相关生长停滞。
DOI：
10.1016/j.jdermsci.2018.05.006
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发表时间：
2018-09
期刊：
影响因子：
--
通讯作者：
Gao XH
中科院分区：
文献类型：
--
作者：
Sun YZ;Ren Y;Zhang YJ;Han Y;Yang Y;Gao YL;Zhu LL;Qi RQ;Chen HD;Gao XH
摘要：背景：热疗是一种有效的治疗癌症和人乳头瘤病毒（HPV）感染的方法。以前的研究表明，热休克蛋白对高温的作用至关重要。目的：研究高温联合DNAJA 4缺乏对人角质形成细胞和尖锐湿疣（CA）组织的影响。方法：HaCaT细胞置于44°C（与37°C相比）水浴中刺激30 min。将从接受包皮环切术或病理检查的患者获得的包皮或CA组织一分为二，并进行类似的处理。用CRISPR/Cas9技术产生DNAJA 4敲除（KO）HaCaT细胞。采用RT-qPCR和Western-blotting检测mRNA和蛋白表达。流式细胞仪分析细胞周期分布、凋亡和衰老。结果：DNAJA 4在HaCaT细胞、包皮和CA组织中受到热处理，在转录和翻译水平上都受到诱导。在HaCaT细胞中，NF-kB，3被高温激活，并且被DNAJA 4缺陷进一步增强。在经受高温的HaCaT细胞中诱导TNF-α4、IL-1B、5、TNFAIP 36和IL-87的转录。DNAJA 4基因敲除可促进TNF-α和IL-1B的表达，而降低TNF α IP 3和IL-8的表达。使用流式细胞术和MTS测定证明细胞存活、增殖和活力降低。此外，NF-kB抑制剂逆转了观察到的大多数表型。结论：高温主要通过NF-κ B依赖性途径降低HaCaT细胞增殖并促进负责抗病毒活性的细胞因子表达。DNAJA 4缺陷增强了HaCaT细胞中热疗对NF-kB的激活，表明DNAJA 4可能是用于治疗皮肤HPV感染的有希望的治疗靶点。
Abstract.BACKGROUND:.Hyperthermia is an effective treatment against cancer and human papillomavirus (HPV) infection. Previous studies have shown that heat shock proteins are crucial to the action of hyperthermia...OBJECTIVES:.To examine the effects of hyperthermia in combination with DNAJA4-deficiency on human keratinocytes and Condyloma acumunatum (CA) tissues...METHODS:.HaCaT cells were subjected to 44°C (compared to 37°C) waterbath for 30min for stimulation. Foreskin or CA tissues obtained from patients undergoing circumcision or pathological examination were bisected and subjected to similar treatments. DNAJA4-knockout (KO) HaCaT cells were generated with CRISPR/Cas9 technology. mRNA and protein expressions were determined using rt-qPCR and western-blotting. Cell cycle distribution, apoptosis and senescence were analyzed by flow cytometry...RESULTS:.DNAJA4 was induced in HaCaT cells, foreskin and CA tissues subjected to hyperthermia at both transcriptional and translational levels. NF-kB,3 was activated by hyperthermia in HaCaT cells, and further enhanced by DNAJA4-deficiency. Transcription of TNF-α4; IL-1B,5 TNFAIP36 and IL-87 were induced in HaCaT cells subjected to hyperthermia. DNAJA4-knockout promoted transcriptions of TNF-α and IL-1B, whereas decreased that of TNFAIP3 and IL-8. Reduced cell survival, proliferation and viability were demonstrated using flow cytometry and MTS assays. Furthermore, NF-kB inhibitors reversed most of the phenotypes observed...CONCLUSIONS:.Hyperthermia reduced HaCaT cell proliferation and promoted cytokine expressions responsible for anti-viral activity, mainly through a NF-kB dependent pathway. DNAJA4-deficiency enhanced the activation of NF-kB by hyperthermia in HaCaT cells, indicating that DNAJA4 may be a promising therapeutic target for use in the treatment of cutaneous HPV infections.
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影响因子：
3.1
作者：
Yi Ren;W. Huo;Rui-Qun Qi;Lanting Hu;Xing-Hua Gao
通讯作者：
Yi Ren;W. Huo;Rui-Qun Qi;Lanting Hu;Xing-Hua Gao
DOI：
10.1073/pnas.95.5.2307
发表时间：
1998-03-03
影响因子：
11.1
作者：
Seitz, CS;Lin, Q;Khavari, PA
通讯作者：
Khavari, PA
DOI：
10.12659/msm.905360
发表时间：
2018-01-01
期刊：
Medical science monitor : international medical journal of experimental and clinical research
影响因子：
--
作者：
Jin Y;Qiu S;Shao N;Zheng J
通讯作者：
Zheng J
影响因子：
--
作者：
Yongbo Liu;Xiaohua Gao;D. Deeb;Yiguan Zhang;J. Shaw;F. Valeriote;S. Gautam
通讯作者：
Yongbo Liu;Xiaohua Gao;D. Deeb;Yiguan Zhang;J. Shaw;F. Valeriote;S. Gautam
DOI：
10.1379/1466-1268(2000)005
发表时间：
2000-04
期刊：
--
影响因子：
--
作者：
V. Volloch;V. Gabai;S. Rits;Thomas Force;M. Sherman
通讯作者：
V. Volloch;V. Gabai;S. Rits;Thomas Force;M. Sherman