Critical roles of TRAIL in hepatic cell death and hepatic inflammation
Shi-Jun Zheng, … , Galit Tsabary, Youhai H. Chen
Shi-Jun Zheng, … , Galit Tsabary, Youhai H. Chen
Published January 1, 2004
Citation Information: J Clin Invest. 2004;113(1):58-64. https://doi.org/10.1172/JCI19255.
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Article Immunology

Critical roles of TRAIL in hepatic cell death and hepatic inflammation

Abstract

The TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis of tumor cells but not most normal cells. Its role in hepatic cell death and hepatic diseases is not clear. In vitro studies suggest that murine hepatocytes are not sensitive to TRAIL-induced apoptosis, indicating that TRAIL may not mediate hepatic cell death. Using two experimental models of hepatitis, we found that hepatic cell death in vivo was dramatically reduced in TRAIL-deficient mice and mice treated with a blocking TRAIL receptor. Although both TRAIL and its death receptor 5 were constitutively expressed in the liver, TRAIL expression by immune cells alone was sufficient to restore the sensitivity of TRAIL-deficient mice to hepatitis. Thus, TRAIL plays a crucial role in hepatic cell death and hepatic inflammation.

Authors

Shi-Jun Zheng, Pu Wang, Galit Tsabary, Youhai H. Chen

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L. monocytogenes counts in the liver and mouse survival rates. (a) Two g...
L. monocytogenes counts in the liver and mouse survival rates. (a) Two groups of BALB/c mice (n = 5) were treated as described in the legend to Figure 6 and sacrificed 1, 3, and 7 days after Listeria infection. The total number of bacteria in the liver and spleen was determined as described in Methods. Results shown are from one representative experiment of four. The differences between the two groups are statistically significant for days 3 and 7 as determined by ANOVA (P < 0.0001). (b) TRAIL+/+ (n = 13) and TRAIL–/– (n = 12) BALB/c mice were infected with 5 × 104 CFUs of L. monocytogenes as described in the legend to Figure 6. Data shown are survival rates of TRAIL+/+ and TRAIL–/– mice pooled from four independent experiments. The difference between the two groups is statistically significant as determined by Mann-Whitney test (P < 0.01).