Mechanism for the release of IL-8 from A549 cells treated with alpha-toxin.

用 α 毒素处理的 A549 细胞释放 IL-8 的机制。

• 批准号: 21790431
• 负责人: ODA Masataka
• 金额: $ 2.58万
• 依托单位: Tokushima Bunri University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21790431/
• 关键词: 病原性; ウエルシュ菌; α毒素; A549細胞; ガングリオシドGM1a; ガングリオシド(GM1); TrkA

A characteristic feature of gas gangrene with Clostridium perfringens(C. perfringens) is the absence of neutrophils within the infected area and the massive accumulation of neutrophils on the vascular endothelium at the margins. Intravenous injection of C. perfringens alpha-toxin into mice resulted in accumulation of neutrophils on the vascular endothelium in lung and liver, and release of GRO/KC. Alpha-toxin triggered activation of signal transduction pathways causing mRNA expression and production of IL-8, which activates migration and binding of neutrophils, in A549 cells. K252a, a tyrosine kinase A(TrkA) inhibitor, and siRNA for TrkA inhibited the toxin-induced phosphorylation of TrkA and production of IL-8.In addition, K252a inhibited the toxin-induced phosphorylation of ERK1/2 and p38 MAPK. PD98059, an ERK1/2 inhibitor, depressed phosphorylation of ERK1/2 and nuclear translocation of NF-κB p65, but SB203580, a p38 MAPK inhibitor, did not. On the other hand, PD98059 and SB203580 suppressed the toxin-induced production of IL-8.Treatment of the cells with PD98059 resulted in inhibition of IL-8 mRNA expression induced by the toxin and that with SB203580 led to a decrease in the stabilization of IL-8 mRNA. These results suggest that alpha-toxin induces production of IL-8 through the activation of two separate pathways, the ERK1/2/NF-κB and p38 MAPK pathways.

产气荚膜梭菌（C。产气荚膜梭菌）的特征是感染区域内缺乏嗜中性粒细胞，并且嗜中性粒细胞在边缘处的血管内皮上大量积聚。静脉注射C.将产气荚膜杆菌α-毒素导入小鼠导致中性粒细胞在肺和肝中的血管内皮上的积累，以及GRO/KC的释放。α-毒素触发信号转导途径的激活，导致mRNA表达和IL-8的产生，其激活A549细胞中中性粒细胞的迁移和结合。酪氨酸激酶A（TrkA）抑制剂K252 a和针对TrkA的siRNA均能抑制毒素诱导的TrkA磷酸化和IL-8的产生; K252 a还能抑制毒素诱导的ERK 1/2和p38 MAPK的磷酸化。ERK 1/2抑制剂PD 98059可抑制ERK 1/2磷酸化和NF-κB p65核转位，而p38 MAPK抑制剂SB 203580则无此作用。PD 98059和SB 203580可抑制毒素诱导的IL-8 mRNA的表达，而SB 203580则可降低毒素诱导的IL-8 mRNA的稳定性。这些结果表明，α-毒素通过激活ERK 1/2/NF-κB和p38 MAPK两条独立途径诱导IL-8的产生。

项目成果

Vizantineのマクロファージ活性化メカニズム

Vizantine巨噬细胞激活机制

• 发表时间: 2011
• 作者: Tumurkhuu G;Koide N;Dagvadorj J;Noman A;Khuda I;Naiki Y;Komatsu T;Yoshida T;Oda M;Nagahama M;Sakurai J;Yokochi T;Oda M;Gantsetseg Tumurkhuu;Masataka Oda;Masahiro Nagahama;Jun Sakurai;小田真隆;永浜政博;小林敬子;小田真隆;樽井敬史;小田真隆;加藤良子;富永かおり;後藤田侑加;南俊宏;田代遼;小林敬子;高田奈央;樽井敬史
• 通讯作者: 樽井敬史

「毒生物はなぜ生み出されたのか?」:二面的多様性とベノミクス

“为什么会产生有毒生物？”：双重多样性和毒液学

• 发表时间: 2011
• 作者: Tumurkhuu G;Koide N;Dagvadorj J;Noman A;Khuda I;Naiki Y;Komatsu T;Yoshida T;Oda M;Nagahama M;Sakurai J;Yokochi T;Oda M;Gantsetseg Tumurkhuu;Masataka Oda;Masahiro Nagahama;Jun Sakurai;小田真隆;永浜政博;小林敬子;小田真隆;樽井敬史;小田真隆;加藤良子;富永かおり;後藤田侑加;南俊宏;田代遼;小林敬子;高田奈央;樽井敬史;高田奈央;南俊宏;田代遼;小田真隆;小田真隆
• 通讯作者: 小田真隆

結核菌由来糖脂質誘導体の抗菌、抗腫瘍作用

结核分枝杆菌糖脂衍生物的抗菌和抗肿瘤作用

• 发表时间: 2010
• 作者: Tumurkhuu G;Koide N;Dagvadorj J;Noman A;Khuda I;Naiki Y;Komatsu T;Yoshida T;Oda M;Nagahama M;Sakurai J;Yokochi T;Oda M;Gantsetseg Tumurkhuu;Masataka Oda;Masahiro Nagahama;Jun Sakurai;小田真隆;永浜政博;小林敬子;小田真隆;樽井敬史;小田真隆;加藤良子;富永かおり;後藤田侑加;南俊宏;田代遼;小林敬子;高田奈央;樽井敬史;高田奈央;南俊宏;田代遼;小田真隆;小田真隆;小田真隆;小田真隆;永浜政博;小田真隆;渋谷昌弘;小田真隆;小田真隆;小田真隆;樋口真美;鈴江綾佳;清家総史;屋比久賢太
• 通讯作者: 屋比久賢太

Role of side-edge site of sphingomyelinase from Bacillus cereus

• DOI: 10.1016/j.bbrc.2012.04.120
• 发表时间: 2012-05-25
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Oda, Masataka;Takahashi, Masaya;Sakurai, Jun
• 通讯作者: Sakurai, Jun

Hemolysis induced by Bacillus cereus sphingomyelinase

蜡样芽胞杆菌鞘磷脂酶诱导的溶血

• 发表时间: 2010
• 期刊: BBA-Biomembranes
• 影响因子: 3.4
• 作者: Oda M;Takahashi M;Matsuno T;Uoo K;Nagahama M;Sakurai J
• 通讯作者: Sakurai J