Novel antagonist antibody to TLR3 blocks poly(I:C)-induced inflammation in vivo and in vitro
Novel antagonist antibody to TLR3 blocks poly(I:C)-induced inflammation in vivo and in vitro
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DOI：
10.1016/j.cellimm.2010.10.008
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发表时间：
2011-01-01
影响因子：
4.3
通讯作者：
Ward, Christine K.
中科院分区：
文献类型：
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作者：
Bunting, Rachel A.;Duffy, Karen E.;Ward, Christine K.
Toll样受体3（TLR 3）结合并响应dsRNA和poly（I：C）（一种合成的双链RNA类似物）发出信号。TLR 3的激活触发先天性应答，其可在病毒感染中或通过炎症放大在免疫介导的炎性疾病中发挥保护或有害作用。生成并表征了两种单克隆抗体CNTO 4685（大鼠抗小鼠TLR 3）和CNTO 5429（CNTO 4685移植到小鼠IgG 1支架上的CDR）。这些mAb结合小鼠TLR 3的细胞外结构域，抑制poly（I：C）诱导的mTLR 3转染的HEK 293 T细胞的活化，并减少poly（I：C）诱导的原代小鼠胚胎成纤维细胞产生CCL 2和CXCL 10。CNTO 5429降低了腹腔内聚（I：C）给药后的血清IL-6和TNF α水平，证明了体内活性。总之，已经产生了特异性抗mTLR 3 mAb以评估小鼠炎症模型中的TLR 3拮抗作用。(C)2010年爱思唯尔公司All rights reserved.
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 TNF alpha 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. (C) 2010 Elsevier Inc. All rights reserved.