Studies on stimulus-specific induction of a novel NF-κB regulator, IκB-ζ, and its physiological roles

新型 NF-κB 调节因子 IκB-ζ 的刺激特异性诱导及其生理作用的研究

• 批准号: 17590252
• 负责人: TAKESHIGE Koichiro
• 金额: $ 2.24万
• 依托单位: KYUSHU UNIVERCITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590252/
• 关键词: Innate Immunity; IκB-ζ; Regulation of Transcription; mRNA Stabilization; Signaling

IκB-ζ is barely detectable in resting macrophages and is strongly induced upon stimulation with lipolysaccharide(LPS) or Interleukin (IL)-1β but not tumor necrosis factor(TNF)-α. The induced IκB-ζ associates with the NF-κB submit in the nucleus and regulates its transcriptional activity both positively and negatively depending on promoter structures of genes. In the present study, we investigated mechanisms that determine the different functions of IκB-ζ and found that IκB-ζ acts as an essential transcriptional activation by forming a complex with NF-κB on promoters harboring the NF-κB and C/EBP binding sites, upon stimulation of Toll-Like receptors or IL-1 receptor. We also analyzed the molecular mechanisms for the differential induction of IκB-ζ and found that the stability of IκB-ζ mRNA is specifically upregulated by stimulation with LPS or IL-1β but not TNF- α and that a 165-bp fragment present in the 3'-UTR of IκB-ζ mRNA confers the stimulus-specific induction and is essential for the induction of IκB-ζ.

静息巨噬细胞中几乎检测不到IκB-ζ，在脂多糖或白介素1β刺激下能强烈诱导，但不能诱导肿瘤坏死因子-α。诱导的I-κB-ζ与核内的核因子-κB结合，根据基因启动子的结构对其转录活性进行正向和负向的调控。在本研究中，我们研究了决定IκB-ζ不同功能的机制，发现IκB-ζ在Toll样受体或IL-1受体的刺激下，通过与含有NF-κB和C/κ结合位点的启动子上的NF-EBP B形成复合体，发挥必要的转录激活作用。我们还分析了IκB-ζ分化诱导的分子机制，发现IκB-ζβ的稳定性可被内毒素或IL-1α特异性上调，但不受肿瘤坏死因子-κ的刺激；IζB-UTR3‘-UTR165bp片段提供刺激特异性诱导，是诱导IκB-ζ所必需的。

项目成果

A missence mutation of the Toll-like receptor 3 gene in a patient with influenza-associated encephalopathy.

流感相关脑病患者中 Toll 样受体 3 基因的错误突变。

• 发表时间: 2005
• 期刊: Clinical Immunology (in press)
• 作者: Hidaka;F.;et al.
• 通讯作者: et al.

Positive and Negative Regulation of Neuclear Factor-κB-mediated Transcription by IκB-ζ an Inducible Nuclear Protein.

IκB-ζ（一种诱导核蛋白）对核因子-κB 介导的转录的正向和负向调节。

• 发表时间: 2005
• 期刊: J.Biol.Chem. 280
• 作者: Motoyama;M.;et al.
• 通讯作者: et al.

誘導型NF-κB制御因子IκB-ζの研究

诱导型NF-κB调节因子IκB-ζ的研究

• 发表时间: 2007
• 期刊: 福岡医学会雑誌 (印刷中)
• 作者: Koyama;H.;Nakamura T;竹重 公一朗
• 通讯作者: 竹重 公一朗

Involvement of p38 MAP kinase in not only activation of the phagocyte NADPH oxidase induced by formyl-methionyl-leucyl-phenylalanine but also determination of the extent of the activity

p38 MAP 激酶不仅参与甲酰甲硫氨酰亮氨酰苯丙氨酸诱导的吞噬细胞 NADPH 氧化酶的激活，而且还参与活性程度的测定

• 发表时间: 2006
• 期刊: Journal of Biochemistry 140
• 作者: Sakamoto;K. et al.
• 通讯作者: K. et al.

A missense mutation of the Toll-like receptor 3 gene in a patient with influenza-associated encephalopathy

• DOI: 10.1016/j.clim.2006.01.005
• 发表时间: 2006-05-01
• 期刊: CLINICAL IMMUNOLOGY
• 影响因子: 8.6
• 作者: Hidaka, F;Matsuo, S;Nunoi, H
• 通讯作者: Nunoi, H