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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TRAIL expression by cells of the immune system is required for the devel...
TRAIL expression by cells of the immune system is required for the development of Con-A–induced hepatitis. TRAIL+/+ or TRAIL–/– liver MNCs (2 × 107 cells per mouse) and splenocytes (3 × 107 cells per mouse) were transferred into TRAIL–/– mice intrahepatically and intrasplenically, respectively. One hour later, mice were injected with Con-A (25 mg/kg of body weight), and serum activities of ALT were assessed 12 hours after the challenge. Data presented are means and SEM of each group (n = 5). Results shown are from one representative experiment of two. The differences between the two groups are statistically significant as determined by ANOVA (P < 0.01).