Agonistic antibody to TLR4/MD-2 protects mice from acute lethal hepatitis induced by TNF-alpha
Akashi-Takamura, S.; Furuta, T.; Takahashi, K.; Tanimura, N.; Kusumoto, Y.; Kobayashi, T.; Saitoh, S-Ichiroh.; Adachi, Y.; Doi, T.; Miyake, K.
Journal of Immunology 176(7): 4244-4251
2006
ISSN/ISBN: 0022-1767 PMID: 16547261 Document Number: 599373
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.