TLR4/MD-2激动性抗体可保护小鼠免受TNF-α诱导的急性致死性肝炎。
Agonistic antibody to TLR4/MD-2 protects mice from acute lethal hepatitis induced by TNF-alpha.
作者信息
Akashi-Takamura Sachiko, Furuta Takahisa, Takahashi Koichiro, Tanimura Natsuko, Kusumoto Yutaka, Kobayashi Toshihiko, Saitoh Shin-Ichiroh, Adachi Yoshiyuki, Doi Takahiro, Miyake Kensuke
机构信息
Division of Infectious Genetics, Institute of Medical Science, University of Tokyo, Japan.
出版信息
J Immunol. 2006 Apr 1;176(7):4244-51. doi: 10.4049/jimmunol.176.7.4244.
LPS is recognized by a heterodimer consisting of TLR4 and its coreceptor MD-2. LPS signal causes excessive inflammation and tissue damage. In this study, we show that a mAb to TLR4/MD-2 protected mice from acute lethal hepatitis caused by LPS/d-galactosamine. The protective effect of the mAb was not due to inhibition of LPS response, because serum TNF-alpha, which was induced by LPS and caused lethal hepatitis, was 10 times up-regulated by the mAb pretreatment. Moreover, this mAb induced antiapoptotic genes in liver in a TLR4/MD-2-dependent manner. These results demonstrated that an agonistic mAb to TLR4/MD-2 protected mice from LPS/d-galactosamine-induced acute lethal hepatitis by delivering a protective signal activating NF-kappaB through TLR4/MD-2.
脂多糖（LPS）由Toll样受体4（TLR4）及其共受体髓样分化蛋白2（MD-2）组成的异二聚体识别。LPS信号会导致过度炎症和组织损伤。在本研究中，我们发现一种针对TLR4/MD-2的单克隆抗体（mAb）可保护小鼠免受LPS/d-半乳糖胺所致的急性致死性肝炎。该mAb的保护作用并非由于抑制LPS反应，因为由LPS诱导并导致致死性肝炎的血清肿瘤坏死因子-α（TNF-α）在mAb预处理后上调了10倍。此外，该mAb以TLR4/MD-2依赖的方式在肝脏中诱导抗凋亡基因。这些结果表明，一种针对TLR4/MD-2的激动性mAb通过传递一个通过TLR4/MD-2激活核因子κB（NF-κB）的保护信号，保护小鼠免受LPS/d-半乳糖胺诱导的急性致死性肝炎。
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