Toll-Like Receptor Ligand-Induced Liver Injury in D-Galactosamine-Sensitized Mice: Differences between TLR7/8 and TLR9 Ligands, Cytokine Patterns, and Cross-Tolerance Induction by TLR2 Ligand Pretreatment.

Toll-Like Receptor Ligand-Induced Liver Injury in D-Galactosamine-Sensitized Mice: Differences between TLR7/8 and TLR9 Ligands, Cytokine Patterns, and Cross-Tolerance Induction by TLR2 Ligand Pretreatment. J Immunol Res. 2017;2017:9653793 Authors: Seki R Abstract Administration of Toll-like receptor ligands (TLRLs) is known to cause liver injury in D-galN-sensitized mice. In the present study, we aimed to complement preceding reports on the TLRL/D-galN system by analyzing comparisons among TLRLs, mouse strain dependence, effects on serum levels of cytokines, and effects of sequential administrations of different TLRLs. In a preliminary set of analyses, we first confirmed that liver failure can be induced by diverse TLRLs, including LTA and R848 in combination with D-galN. Analysis using TLR4-deficient mice excluded potential confounding effects of endogenous TLR4Ls that include those referred to as DAMPs in CpG DNA/D-galN hepatotoxicity. Subsequently, we showed that LTA pretreatment could prevent mortality in both CpG DNA/D-galN- and R848/D-galN-treated mice compared to without pretreatment. Incidentally, we observed that without the LTA pretreatment, CpG DNA/D-galN showed relatively higher liver-specific toxicity whereas R848/D-galN showed more symptoms of multiple organ failure. These findings suggest that, in D-galN-sensitized mice, different TLRLs not only show similarity in the ability to induce hepatic injury but also exhibit d...
Source: Journal of Immunology Research - Category: Allergy & Immunology Tags: J Immunol Res Source Type: research