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Apoptosis of macrophages and T cells in periodontal tissues : Its molecular mechanisms and biological roles

牙周组织巨噬细胞和T细胞凋亡的分子机制和生物学作用

基本信息

批准号：
06454528
负责人：
KIZAKI Harutoshi
金额：
$ 4.54万
依托单位：
TOKYO DENTAL COLLEGE
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454528/
关键词：
Periodontitis Apoptosis Monocytes Macrophages T cells Thymocytes Tyrosine phosphorylation LPS 歯周組織分子機構

项目摘要

Apoptosis is a physiological cell death process of eliminating unwanted cells from living organisms during embryogenic and adult development. It also function in regulation of survival of inflammatory cells in chronic inflammatory lesions. The aims of the present study are to elucidate the molecular mechanisms and roles of apoptosis of monocytes, macrophages and T cells which play important roles in periodontitis. Thymocyte apoptosis is found to be regulated by at least two steps of protein phosphorylation ; one is triggering apoptosis, another is involved in progressing apoptosis. The latter protein phosphorylation occurs at a later stage of the process and seems to be common to the apoptosis induced by various stimuli. Thymocyte apoptosis induced by various stimuli was inhibited by inhibitors of proteasome, suggesting an important role of proteases in apoptosis. Apoptosis induced by dexamethasone in spleen T cells was paritially inhibited by cycloheximide, though cycloheximide itself … More induced apoptosis. Thus, there exist two mechanisms of apoptosis in mature T cells, protein synthesis-dependent and-independent. Spleen T cells were resistant to TPA or A23187 which was able to induce apoptosis in thymocytes. However, T cells bacame relatively sensitive to A23187 after cultivation for 3 days in the presence of IL-2, suggesting that activation-induced cell death is induced in part by calcium-mediated signaling. IL-2-dependent CTLL-2 cells underwent apoptosis when IL-2 was withdrawn accompanying by decreased in protein tyrosine phosphorylation in nuclear protein. Depletion of IL-2 is a cause of activation-induced cell death which participates in resolution of inflammation. Further studies on the molecular mechanisms of apoptosis in thymocytes and T cells are required. Monocyte and macroophage cell lines, U937 and P388D1 cells underwent apoptosis when serum was depleted. The apoptosis was inhibited by TNF-alpha or substance P accompanying by increased protein tyrosine phosphorylation. The results suggest cytokines or neuropeptides modualate inflammatory responses through regulating survival of inflammatory cells. Less

细胞凋亡是生物体在胚胎发生和成体发育过程中清除无用细胞的生理性细胞死亡过程。它还在慢性炎性病变中调节炎性细胞的存活。本研究的目的是阐明在牙周炎中起重要作用的单核细胞、巨噬细胞和T细胞凋亡的分子机制和作用。胸腺细胞凋亡至少受两个蛋白磷酸化步骤的调控，一个是触发凋亡，另一个是参与进行性凋亡。后一种蛋白磷酸化发生在该过程的后期，并且似乎是由各种刺激诱导的细胞凋亡所共有的。蛋白酶体抑制剂可抑制各种刺激诱导的胸腺细胞凋亡，表明蛋白酶在细胞凋亡中发挥重要作用。放线菌酮可部分抑制地塞米松诱导的脾T细胞凋亡， ...更多信息诱导凋亡。因此，在成熟T细胞中存在两种凋亡机制，蛋白质合成依赖性和非依赖性。脾T细胞对TPA或A23187具有抗性，TPA或A23187能够诱导胸腺细胞凋亡。然而，在IL-2存在下培养3天后，T细胞对A23187相对敏感，表明活化诱导的细胞死亡部分由钙介导的信号传导诱导。IL-2依赖的CTLL-2细胞在IL-2撤除后发生凋亡，同时伴有核蛋白酪氨酸磷酸化水平降低。IL-2的消耗是参与炎症消退的活化诱导的细胞死亡的原因。胸腺细胞和T细胞凋亡的分子机制有待进一步研究。单核细胞和巨噬细胞系，U937和P388 D1细胞在血清耗尽时发生凋亡。TNF-α或P物质可抑制细胞凋亡，并伴有蛋白酪氨酸磷酸化增加。这些结果表明细胞因子或神经肽通过调节炎性细胞的存活来调节炎症反应。少