Agonistic antibody to TLR4/MD-2 protects mice from acute lethal hepatitis induced by TNF-α

被引：28

作者：

Akashi-Takamura, Sachiko

Furuta, Takahisa

Takahashi, Koichiro

Tanimura, Natsuko

Kusumoto, Yutaka

Kobayashi, Toshihiko

Saitoh, Shin-ichiroh

Adachi, Yoshiyuki

Doi, Takahiro

Miyake, Kensuke

机构：

[1] Univ Tokyo, Inst Med Sci, Div Infect Genet, Minato Ku, Tokyo 1088639, Japan

[2] Japan Sci & Technol, Core Res Engn Sci & Technol, Tokyo, Japan

[3] Tokyo Univ Pharm & Life Sci, Sch Pharm, Lab Immunopharmacol Microbial Prod, Tokyo, Japan

[4] RIKEN, Tsukuba Inst, Bioresource Ctr, Subteam BioSignal Integrat,Technol & dev Team Bio, Ibaraki, Japan

来源：

JOURNAL OF IMMUNOLOGY | 2006年 / 176卷 / 07期

关键词：

D O I：

10.4049/jimmunol.176.7.4244

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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-kappa B through TLR4/MD-2.

引用

页码：4244 / 4251

页数：8

共 34 条

[1] Lipopolysaccharide interaction with cell surface toll-like receptor 4-MD-2: Higher affinity than that with MD-2 or CD14 [J].