Pulmonary collectin regulates drug-induced lung injury.

肺集合素调节药物引起的肺损伤。

• 批准号: 20590930
• 负责人: TAKAHASHI Hiroki
• 金额: $ 3万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590930/
• 关键词: 薬剤性肺障害; ブレオマイシン; 肺コレクチン; 肺サーファクタント蛋白質A; トル様受容体; SP-A; TLR2; ノックアウトマウス; 肺線維化

The purposes of this project were to investigate the mechanisms of regulation by which lung collectins, surfactant proteins A and D (SP-A and SP-D), and Toll-like receptor (TLR) function against inflammation on the development of drug induced lung injury, and to establish the molecular basis for the clinical application of these proteins. First, the mouse model of lung injury was established using drugs, and SP-A^<-/-> mice had significantly higher mortality rates than WT mice. SP-A inhibited drug-induced inflammatory cytokine production from rat alveolar macrophages. SP-A blocked sTLR2-bleomycin binding in the dose dependent manner. These results suggest that bleomycin signals are transmitted through TLR2 dependent pathway and regulated by the molecular interaction of SP-A.

该项目的目的是研究肺集合素、表面活性蛋白 A 和 D（SP-A 和 SP-D）以及 Toll 样受体（TLR）在药物诱导肺发展过程中对抗炎症的调节机制。损伤，并为这些蛋白的临床应用建立分子基础。首先，采用药物建立小鼠肺损伤模型，SP-A^-/->小鼠的死亡率明显高于WT小鼠。 SP-A 抑制药物诱导的大鼠肺泡巨噬细胞产生炎症细胞因子。 SP-A 以剂量依赖性方式阻断 sTLR2-博莱霉素结合。这些结果表明博来霉素信号通过TLR2依赖性途径传递并受到SP-A的分子相互作用的调节。

项目成果

Vpr induces TLR4/MyD88-mediated IL-6 production and reactivates viral production from latency.

Vpr 诱导 TLR4/MyD88 介导的 IL-6 产生并从潜伏期重新激活病毒产生。

• 发表时间: 2010
• 作者: Hoshino S; Kuroki Y; et al.
• 通讯作者: et al.

Pulmonary surfactant protein D binds MD-2 through the carbohydrate recognition domain.

肺表面活性剂蛋白 D 通过碳水化合物识别域结合 MD-2。

• 发表时间: 2008
• 作者: Nie X; Nishitani C; Yamazoe M; Ariki S; Takahashi M; Shimizu T; Mitsuzawa H; Sawada K; Smith K; Crouch E; Nagae H; Takahashi H; Kuroki Y.
• 通讯作者: Kuroki Y.

Surfactant protein D in sera as a prognostic factor of idiopathic pulmonary fibrosis.

血清中的表面活性蛋白 D 作为特发性肺纤维化的预后因素。

• 发表时间: 2008
• 作者: Shiratori M; Kanai A; Otsuka M; Chiba H; Takahashi H.
• 通讯作者: Takahashi H.

Increasing antiviral activity of surfactant protein d trimers by introducing residues from bovine serum collectins : dissociation of mannan-binding and antiviral activity

通过引入牛血清集合素残基提高表面活性蛋白 d 三聚体的抗病毒活性：甘露聚糖结合的解离和抗病毒活性

• 发表时间: 2010
• 影响因子: 3.7
• 作者: Hartshorn KL; Kuroki Y; et al.
• 通讯作者: et al.

Surfactant protein A modulate bleomycin-induced lung injury in toll-like receptor 2 dependent pathway

表面活性剂蛋白 A 通过 Toll 样受体 2 依赖性途径调节博莱霉素诱导的肺损伤

• 发表时间: 2010
• 作者: Kuronuma K; Takahashi H; et al
• 通讯作者: et al