CpG DNA prevents liver injury and shock-mediated death by modulating expression of interleukin-1 receptor-associated kinases.

ABSTRACT: Tumor necrosis factor-alpha (TNF-alpha) produced by macrophages in response to CpG DNA induces severe liver injury and subsequent death of D-galactosamine (D-GalN)-sensitized mice. In the present study we demonstrate that mice pre-exposed to CpG DNA are resistant to liver injury and death induced by CpG DNA/D-GalN. CpG DNA/D-GalN failed to induce TNF-alpha production and hepatocyte apoptosis in the mice pre-exposed to CpG DNA. In addition, macrophages isolated from the CpG DNA-pretreated mice showed suppressed activation of MAPKs and NF-kappaB and production of TNF-alpha in response to CpG DNA, indicating that the CpG DNA-mediated protection of CpG DNA/D-GalN-challenged mice is due to the hyporesponsiveness of macrophages to CpG DNA. CpG DNA pretreatment in vivo inhibited expression of int

SUBMITTER: Kim YI 

PROVIDER: S-EPMC2397458 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature