Kupffer cell inactivation ameliorates immune liver injury via TNF-α/TNFR1 signal pathway in trichloroethylene sensitized mice.

METHODS

36 female BALB/c mice were selected and randomly divided the mice into four groups. We established a BALB/c mouse model of TCE sensitization and pretreatment with GdCl3 (40 mg/kg) by intraperitoneal injection during the during the 17th and 19th days.

RESULTS

We found F4/80, the marker of Kupffer cell, was increased in TCE positive group. GdCl3 treatment successfully blocked the activation of Kupffer cell. TNF-α was increased significantly in liver of TCE sensitized mice and decreased significantly when low-dose GdCl3 was used. We found TNF receptor 1 (TNFR1) was increased significantly and GdCl3 treatment resumed the expression of TNFR1 to normal level, as well as the F4/80, TNF-α and TNFR1 mRNA. We also found both caspase-8 and caspase-3 increased in TCE positive group and decreased in TCE + GdCl3 positive group. The number of apoptotic cells in TCE sensitized mice increased by TUNEL staining, and GdCl3 treatment alleviated this increase. Some cells showed edema and inflammatory cell aggregation in liver of TCE positive group, while in the TCE + GdCl3 positive group, the cytoplasm became loose and vacuole-like degeneration occurred.

CONCLUSION

Our study unveils cross-talk between Kupffer cell activation and TNFR1 which mediate apoptosis in liver of TCE sensitized mice.