Periodontal Treatment by Regulation of Novel TNF-α Transcription Factor in Monocytes

通过调节单核细胞中新型 TNF-α 转录因子进行牙周治疗

基本信息

批准号：
12470471
负责人：
TAKASHIBA Shogo
金额：
$ 8.38万
依托单位：
OKAYAMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470471/
关键词：
Periodontal disease TNF Regulation of Gene Transcription Local Gene Delivery Anti-inflammatory Therapy

项目摘要

Lipopolysaccharide (LPS) is a potent stimulator of monocytes and macrophages, causing secretion of tumor necrosis factor alpha (TNF-α). It gives the deleterious effects to the host of TNF-α, especially advance of inflammation, the destruction of the tissue. It also gives same effects in the periodontal tissue.We tried to control TNF-α gene transcription not using NF-κB strongly concerned with other activities of the cells but using LITAF (LPS-induced TNF-α factor) which we identified as a new transcription factor of its transcription. We found that inhibition of LITAF mRNA expression in THP-1 cells resulted in a reduction of TNF-α transcription.We could find strong LITAF promoter region by LPS stimulation and same consensus sequences as NF-IL6 and AP-1 in this region. On the other hand, we found LITAF localization because staining for LITAF was present in the nuclei of THP-1 after LPS stimulation. We also established gene transfection to find the best method for transfection in vivo.In addition, we transfected mutants of 1κB-α which is one of the inhibitor of NF-κB into the THP-1 cells. We established only the sysyem of THP-1 cells without NF-κB influence, however we will discussed the influence of TNF-α expression by LITAF and the effect of LITAF without NF-κB even though this research period was over.

脂多糖（LPS）是单核细胞和巨噬细胞的潜在刺激剂，导致肿瘤坏死因子α（TNF-α）的分泌。它给TNF-α的宿主带来了有害影响，尤其是感染的前进，是组织的破坏。它在牙周组织中也产生了相同的作用。我们试图控制不使用NF-κB的TNF-α基因转录，这与细胞的其他活性密切相关，而是使用LITAF（LPS诱导的TNF-α因子），我们将其确定为其转录的新转录因子。我们发现，THP-1细胞中LITAF mRNA表达的抑制作用导致TNF-α转录的减少。我们可以通过LPS刺激和与NF-IL6和AP-1相同的LITAF启动子区域和相同的共识序列找到强的LITAF启动子区域。另一方面，我们发现LITAF的定位是因为LITAF的染色在LPS刺激后的THP-1核中存在。我们还建立了基因转化，以找到体内转化的最佳方法。此外，我们翻译了1κB-α的突变体，这是NF-κB的抑制剂之一，转化为THP-1细胞。我们仅建立了没有NF-κB影响的THP-1细胞的Sysyem，但是我们将讨论LITAF的TNF-α表达的影响，即使该研究期结束了，LITAF和没有NF-κB的效果也是如此。