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首页> 外文期刊>Cellular immunology >Novel antagonist antibody to TLR3 blocks poly(I:C)-induced inflammation in vivo and in vitro.
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Novel antagonist antibody to TLR3 blocks poly(I:C)-induced inflammation in vivo and in vitro.

机译:TLR3嵌段的新型拮抗剂抗体聚(I:C) - 诱导体内和体外炎症。

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摘要

Toll-like receptor 3 (TLR3) binds and signals in response to dsRNA and poly(I:C), a synthetic double stranded RNA analog. Activation of TLR3 triggers innate responses that may play a protective or detrimental role in viral infections or in immune-mediated inflammatory diseases through amplification of inflammation. Two monoclonal antibodies, CNTO4685 (rat anti-mouse TLR3) and CNTO5429 (CDRs from CNTO4685 grafted onto a mouse IgG1 scaffold) were generated and characterized. These mAbs bind the extracellular domain of mouse TLR3, inhibit poly(I:C)-induced activation of HEK293T cells transfected with mTLR3, and reduce poly(I:C)-induced production of CCL2 and CXCL10 by primary mouse embryonic fibroblasts. CNTO5429 decreased serum IL-6 and TNFalpha levels post-intraperitoneal poly(I:C) administration, demonstrating in vivo activity. In summary, specific anti-mTLR3 mAbs have been generated to assess TLR3 antagonism in mouse models of inflammation.
机译:Toll样受体3(TLR3)响应于DSRNA和Poly(I:C)结合和信号,合成双链RNA类似物。 激活TLR3触发在病毒感染或通过扩增炎症的病毒感染或免疫介导的炎性疾病中可能发挥保护或不利的反应。 产生两种单克隆抗体,CNTO4685(大鼠抗小鼠TLR3)和CNTO5429(来自接枝到小鼠IgG1支架上的CNTO4685的CDRS)。 这些MAb结合小鼠TLR3的细胞外结构域,抑制聚(I:C) - 诱导用MTLR3转染的HEK293T细胞的活化,并通过原发小鼠胚胎成纤维细胞减少聚(I:C)诱导CCL2和CXC110的产生。 CNTO5429减少了腹膜内聚(I:C)给药后的血清IL-6和TNFalpha水平,展示体内活性。 总之,已经产生了特异性抗MTLR3 mAb以评估炎症的小鼠模型中的TLR3拮抗作用。

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