SB-431542，一种转化生长因子β抑制剂，会损害克氏锥虫在心肌细胞中的感染及寄生虫周期的完成。
SB-431542, a transforming growth factor beta inhibitor, impairs Trypanosoma cruzi infection in cardiomyocytes and parasite cycle completion.
作者信息
Waghabi Mariana C, Keramidas Michelle, Calvet Claudia M, Meuser Marcos, de Nazaré C Soeiro Maria, Mendonça-Lima Leila, Araújo-Jorge Tania C, Feige Jean-Jacques, Bailly Sabine
机构信息
Laboratorio de Genômica Funcional e Bioinformática, Departamento de Bioquímica e Biologia Molecular, Instituto Oswaldo Cruz, Brasil, Rio de Janeiro, RJ, Brazil.
出版信息
Antimicrob Agents Chemother. 2007 Aug;51(8):2905-10. doi: 10.1128/AAC.00022-07. Epub 2007 May 25.
Abstract
The antiinflammatory cytokine transforming growth factor beta (TGF-beta) plays an important role in Chagas disease, a parasitic infection caused by the protozoan Trypanosoma cruzi. In the present study, we show that SB-431542, an inhibitor of the TGF-beta type I receptor (ALK5), inhibits T. cruzi-induced activation of the TGF-beta pathway in epithelial cells and in cardiomyocytes. Further, we demonstrate that addition of SB-431542 greatly reduces cardiomyocyte invasion by T. cruzi. Finally, SB-431542 treatment significantly reduces the number of parasites per infected cell and trypomastigote differentiation and release. Taken together, these data further confirm the major role of the TGF-beta signaling pathway in both T. cruzi infection and T. cruzi cell cycle completion. Our present data demonstrate that small inhibitors of the TGF-beta signaling pathway might be potential pharmacological tools for the treatment of Chagas disease.
摘要
抗炎细胞因子转化生长因子β（TGF-β）在恰加斯病中起重要作用，恰加斯病是一种由原生动物克氏锥虫引起的寄生虫感染。在本研究中，我们发现I型TGF-β受体（ALK5）的抑制剂SB-431542可抑制克氏锥虫诱导的上皮细胞和心肌细胞中TGF-β信号通路的激活。此外，我们证明添加SB-431542可大大减少克氏锥虫对心肌细胞的侵袭。最后，SB-431542处理显著减少了每个感染细胞中的寄生虫数量以及锥鞭毛体的分化和释放。综上所述，这些数据进一步证实了TGF-β信号通路在克氏锥虫感染和克氏锥虫细胞周期完成中的主要作用。我们目前的数据表明，TGF-β信号通路的小分子抑制剂可能是治疗恰加斯病的潜在药理学工具。
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本文引用的文献
1
Inhibitor-resistant type I receptors reveal specific requirements for TGF-beta signaling in vivo.抑制剂抗性I型受体揭示了体内TGF-β信号传导的特定要求。
Dev Biol. 2006 Jul 15;295(2):730-42. doi: 10.1016/j.ydbio.2006.03.050. Epub 2006 May 8.
2
The logic of TGFbeta signaling.转化生长因子β信号传导的逻辑
FEBS Lett. 2006 May 22;580(12):2811-20. doi: 10.1016/j.febslet.2006.04.033. Epub 2006 Apr 21.
3
Fibrosis in heart disease: understanding the role of transforming growth factor-beta in cardiomyopathy, valvular disease and arrhythmia.心脏病中的纤维化：了解转化生长因子-β在心肌病、瓣膜病和心律失常中的作用。
Immunology. 2006 May;118(1):10-24. doi: 10.1111/j.1365-2567.2006.02336.x.
4
Uptake of host cell transforming growth factor-beta by Trypanosoma cruzi amastigotes in cardiomyocytes: potential role in parasite cycle completion.克氏锥虫无鞭毛体在心肌细胞中摄取宿主细胞转化生长因子-β：在寄生虫生命周期完成中的潜在作用。
Am J Pathol. 2005 Oct;167(4):993-1003. doi: 10.1016/s0002-9440(10)61189-3.
5
Activation of transforming growth factor beta by Trypanosoma cruzi.克氏锥虫对转化生长因子β的激活作用
Cell Microbiol. 2005 Apr;7(4):511-7. doi: 10.1111/j.1462-5822.2004.00481.x.
6
Inhibition of TGF-beta signaling by an ALK5 inhibitor protects rats from dimethylnitrosamine-induced liver fibrosis.ALK5抑制剂对转化生长因子-β信号通路的抑制作用可保护大鼠免受二甲基亚硝胺诱导的肝纤维化。
Br J Pharmacol. 2005 May;145(2):166-77. doi: 10.1038/sj.bjp.0706172.
7
Progressive transforming growth factor beta1-induced lung fibrosis is blocked by an orally active ALK5 kinase inhibitor.进展性转化生长因子β1诱导的肺纤维化被一种口服活性ALK5激酶抑制剂阻断。
Am J Respir Crit Care Med. 2005 Apr 15;171(8):889-98. doi: 10.1164/rccm.200405-612OC. Epub 2004 Nov 24.
8
Chagas disease: current epidemiological trends after the interruption of vectorial and transfusional transmission in the Southern Cone countries.恰加斯病：南锥体国家病媒传播和输血传播中断后的当前流行病学趋势
Mem Inst Oswaldo Cruz. 2003 Jul;98(5):577-91. doi: 10.1590/s0074-02762003000500001. Epub 2003 Sep 8.
9
Host and parasite apoptosis following Trypanosoma cruzi infection in in vitro and in vivo models.克氏锥虫感染的体外和体内模型中宿主与寄生虫的凋亡
Cell Tissue Res. 2003 Nov;314(2):223-35. doi: 10.1007/s00441-003-0782-5. Epub 2003 Aug 20.
10
Implication of transforming growth factor-beta1 in Chagas disease myocardiopathy.转化生长因子-β1在恰加斯病心肌病中的作用
J Infect Dis. 2002 Dec 15;186(12):1823-8. doi: 10.1086/345882. Epub 2002 Nov 22.
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