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RESPONSES OF NORMAL HUMAN KERATINOCYTES TO CYTOKINES

正常人角质形成细胞对细胞因子的反应

基本信息

批准号：
6474600
负责人：
John R. Basile
金额：
$ 20.82万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-07-01 至 2002-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6474600
关键词：
RESPONSES NORMAL HUMAN KERATINOCYTES CYTOKINES

项目摘要

I am currently working in the laboratory of Dr. Karl Munger attempting to characterize the nature of the responses of normal human keratinocytes to the cytokines TNF-alpha and TRAIL. Through their respective receptors, these cytokines can alternately cause growth arrest or apoptosis, depending upon conditions. Dr. Munger's lab studies the effects of the human papillomavirus on cell cycle control. This virus, whose natural host is the keratinocyte, attempts to take over control of the cell by expressing proteins which interfere with regulation of the natural cycle of cell growth and division. This permits the virus to use cellular machinery to replicate its own viral genome at the expense of the cell itself. These viral proteins also have the effect of altering an infected cell's responses to the protective cytokines produced by the body to defend against just such an infection. Among these cytokines are TNF-alpha and TRAIL. At this point in my research, I have discovered that human keratinocytes exhibit a dramatic growth arrest in response to small amounts of TNF-alpha and TRAIL alone and an apoptotic response when these compounds are combined with protein synthesis inhibitor cycloheximide. In the second phase of my research I will transfect papillomavirus oncoproteins into keratinocytes in an attempt to recognize changes in the growth arrest and apoptotic responses to TNF-alpha and TRAIL. I also will characterize changes in mRNA expression and stability of some of the proteins involved in cell cycle control.

我目前在卡尔·芒格博士的实验室工作，来描述正常人的反应角质形成细胞对细胞因子TNF-α和TRAIL的反应。通过他们这些细胞因子可以交替地引起生长，停滞或凋亡，取决于条件。博士芒格的实验室研究了人类乳头瘤病毒对细胞的影响，循环控制这种病毒的天然宿主是角质细胞，试图通过表达蛋白质来控制细胞，干扰细胞生长的自然周期的调节，师. 这使得病毒能够利用细胞机制进行复制以细胞本身为代价来复制病毒基因组。这些病毒蛋白质也有改变受感染细胞反应的作用身体产生的保护性细胞因子来抵御这样的感染。这些细胞因子包括TNF-α和TRAIL。在我的研究中，我发现人类角质细胞表现出显著的生长停滞，以应对少量的单独的TNF-α和TRAIL以及当这些化合物与蛋白质合成抑制剂放线菌酮组合。在我研究的第二阶段，我将检测乳头瘤病毒，癌蛋白进入角质形成细胞，试图识别对TNF-α和TRAIL的生长停滞和凋亡反应。我还将描述一些细胞的mRNA表达和稳定性的变化，参与细胞周期控制的蛋白质。