TRAIL mediates liver injury by the innate immune system in the bile duct-ligated mouse

Alisan Kahraman, Fernando J. Barreyro, Steven F. Bronk, Nathan W. Werneburg, Justin L. Mott, Yuko Akazawa, Howard C. Masuoka, Charles L Howe, Gregory James Gores

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

The contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a death ligand expressed by cells of the innate immune system, to cholestatic liver injury has not been explored. Our aim was to ascertain if TRAIL contributes to liver injury in the bile duct-ligated (BDL) mouse. C57/BL6 wild-type (wt), TRAIL heterozygote (TRAIL+/-), and TRAIL knockout (TRAIL-/-) mice were used for these studies. Liver injury and fibrosis were examined 7 and 14 days after BDL, respectively. Hepatic TRAIL messenger RNA (mRNA) was 6-fold greater in BDL animals versus sham-operated wt animals (P < 0.01). The increased hepatic TRAIL expression was accompanied by an increase in liver accumulation of natural killer 1.1 (NK 1.1)-positive NK and natural killer T (NKT) cells, the predominant cell types expressing TRAIL. Depletion of NK 1.1-positive cells reduced hepatic TRAIL mRNA expression and serum alanine aminotransferase (ALT) values. Consistent with a role for NK/NKT cells in this model of liver injury, stress ligands necessary for their recognition of target cells were also up-regulated in hepatocytes following BDL. Compared to sham-operated wt mice, BDL mice displayed a 13-fold increase in terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and an 11-fold increase in caspase 3/7-positive hepatocytes (P < 0.01). The number of TUNEL and caspase 3/7-positive cells was reduced by > 80% in BDL TRAIL knockout animals (P < 0.05). Likewise, liver histology, number of bile infarcts, serum ALT values, hepatic fibrosis, and animal survival were also improved in BDL TRAIL-/- animals as compared to wt animals. Conclusion: These observations support a pivotal role for TRAIL in cholestatic liver injury mediated by NK 1.1-positive NK/NKT cells.

Original languageEnglish (US)
Pages (from-to)1317-1330
Number of pages14
JournalHepatology
Volume47
Issue number4
DOIs
StatePublished - Apr 2008

Fingerprint

Bile Ducts
Immune System
Liver
Wounds and Injuries
Wild Animals
Ligands
Natural Killer T-Cells
Heterozygote
Knockout Mice
Bile
Natural Killer Cells
Liver Cirrhosis
Histology
Fibrosis
Tumor Necrosis Factor-alpha
Apoptosis
Messenger RNA
Serum

ASJC Scopus subject areas

  • Hepatology

Cite this

Kahraman, A., Barreyro, F. J., Bronk, S. F., Werneburg, N. W., Mott, J. L., Akazawa, Y., ... Gores, G. J. (2008). TRAIL mediates liver injury by the innate immune system in the bile duct-ligated mouse. Hepatology, 47(4), 1317-1330. https://doi.org/10.1002/hep.22136

TRAIL mediates liver injury by the innate immune system in the bile duct-ligated mouse. / Kahraman, Alisan; Barreyro, Fernando J.; Bronk, Steven F.; Werneburg, Nathan W.; Mott, Justin L.; Akazawa, Yuko; Masuoka, Howard C.; Howe, Charles L; Gores, Gregory James.

In: Hepatology, Vol. 47, No. 4, 04.2008, p. 1317-1330.

Research output: Contribution to journalArticle

Kahraman, A, Barreyro, FJ, Bronk, SF, Werneburg, NW, Mott, JL, Akazawa, Y, Masuoka, HC, Howe, CL & Gores, GJ 2008, 'TRAIL mediates liver injury by the innate immune system in the bile duct-ligated mouse', Hepatology, vol. 47, no. 4, pp. 1317-1330. https://doi.org/10.1002/hep.22136
Kahraman A, Barreyro FJ, Bronk SF, Werneburg NW, Mott JL, Akazawa Y et al. TRAIL mediates liver injury by the innate immune system in the bile duct-ligated mouse. Hepatology. 2008 Apr;47(4):1317-1330. https://doi.org/10.1002/hep.22136
Kahraman, Alisan ; Barreyro, Fernando J. ; Bronk, Steven F. ; Werneburg, Nathan W. ; Mott, Justin L. ; Akazawa, Yuko ; Masuoka, Howard C. ; Howe, Charles L ; Gores, Gregory James. / TRAIL mediates liver injury by the innate immune system in the bile duct-ligated mouse. In: Hepatology. 2008 ; Vol. 47, No. 4. pp. 1317-1330.
@article{1c2bcf0102584a1d8d092bb0617b6cfd,
title = "TRAIL mediates liver injury by the innate immune system in the bile duct-ligated mouse",
abstract = "The contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a death ligand expressed by cells of the innate immune system, to cholestatic liver injury has not been explored. Our aim was to ascertain if TRAIL contributes to liver injury in the bile duct-ligated (BDL) mouse. C57/BL6 wild-type (wt), TRAIL heterozygote (TRAIL+/-), and TRAIL knockout (TRAIL-/-) mice were used for these studies. Liver injury and fibrosis were examined 7 and 14 days after BDL, respectively. Hepatic TRAIL messenger RNA (mRNA) was 6-fold greater in BDL animals versus sham-operated wt animals (P < 0.01). The increased hepatic TRAIL expression was accompanied by an increase in liver accumulation of natural killer 1.1 (NK 1.1)-positive NK and natural killer T (NKT) cells, the predominant cell types expressing TRAIL. Depletion of NK 1.1-positive cells reduced hepatic TRAIL mRNA expression and serum alanine aminotransferase (ALT) values. Consistent with a role for NK/NKT cells in this model of liver injury, stress ligands necessary for their recognition of target cells were also up-regulated in hepatocytes following BDL. Compared to sham-operated wt mice, BDL mice displayed a 13-fold increase in terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and an 11-fold increase in caspase 3/7-positive hepatocytes (P < 0.01). The number of TUNEL and caspase 3/7-positive cells was reduced by > 80{\%} in BDL TRAIL knockout animals (P < 0.05). Likewise, liver histology, number of bile infarcts, serum ALT values, hepatic fibrosis, and animal survival were also improved in BDL TRAIL-/- animals as compared to wt animals. Conclusion: These observations support a pivotal role for TRAIL in cholestatic liver injury mediated by NK 1.1-positive NK/NKT cells.",
author = "Alisan Kahraman and Barreyro, {Fernando J.} and Bronk, {Steven F.} and Werneburg, {Nathan W.} and Mott, {Justin L.} and Yuko Akazawa and Masuoka, {Howard C.} and Howe, {Charles L} and Gores, {Gregory James}",
year = "2008",
month = "4",
doi = "10.1002/hep.22136",
language = "English (US)",
volume = "47",
pages = "1317--1330",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "4",

}

TY - JOUR

T1 - TRAIL mediates liver injury by the innate immune system in the bile duct-ligated mouse

AU - Kahraman, Alisan

AU - Barreyro, Fernando J.

AU - Bronk, Steven F.

AU - Werneburg, Nathan W.

AU - Mott, Justin L.

AU - Akazawa, Yuko

AU - Masuoka, Howard C.

AU - Howe, Charles L

AU - Gores, Gregory James

PY - 2008/4

Y1 - 2008/4

N2 - The contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a death ligand expressed by cells of the innate immune system, to cholestatic liver injury has not been explored. Our aim was to ascertain if TRAIL contributes to liver injury in the bile duct-ligated (BDL) mouse. C57/BL6 wild-type (wt), TRAIL heterozygote (TRAIL+/-), and TRAIL knockout (TRAIL-/-) mice were used for these studies. Liver injury and fibrosis were examined 7 and 14 days after BDL, respectively. Hepatic TRAIL messenger RNA (mRNA) was 6-fold greater in BDL animals versus sham-operated wt animals (P < 0.01). The increased hepatic TRAIL expression was accompanied by an increase in liver accumulation of natural killer 1.1 (NK 1.1)-positive NK and natural killer T (NKT) cells, the predominant cell types expressing TRAIL. Depletion of NK 1.1-positive cells reduced hepatic TRAIL mRNA expression and serum alanine aminotransferase (ALT) values. Consistent with a role for NK/NKT cells in this model of liver injury, stress ligands necessary for their recognition of target cells were also up-regulated in hepatocytes following BDL. Compared to sham-operated wt mice, BDL mice displayed a 13-fold increase in terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and an 11-fold increase in caspase 3/7-positive hepatocytes (P < 0.01). The number of TUNEL and caspase 3/7-positive cells was reduced by > 80% in BDL TRAIL knockout animals (P < 0.05). Likewise, liver histology, number of bile infarcts, serum ALT values, hepatic fibrosis, and animal survival were also improved in BDL TRAIL-/- animals as compared to wt animals. Conclusion: These observations support a pivotal role for TRAIL in cholestatic liver injury mediated by NK 1.1-positive NK/NKT cells.

AB - The contribution of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a death ligand expressed by cells of the innate immune system, to cholestatic liver injury has not been explored. Our aim was to ascertain if TRAIL contributes to liver injury in the bile duct-ligated (BDL) mouse. C57/BL6 wild-type (wt), TRAIL heterozygote (TRAIL+/-), and TRAIL knockout (TRAIL-/-) mice were used for these studies. Liver injury and fibrosis were examined 7 and 14 days after BDL, respectively. Hepatic TRAIL messenger RNA (mRNA) was 6-fold greater in BDL animals versus sham-operated wt animals (P < 0.01). The increased hepatic TRAIL expression was accompanied by an increase in liver accumulation of natural killer 1.1 (NK 1.1)-positive NK and natural killer T (NKT) cells, the predominant cell types expressing TRAIL. Depletion of NK 1.1-positive cells reduced hepatic TRAIL mRNA expression and serum alanine aminotransferase (ALT) values. Consistent with a role for NK/NKT cells in this model of liver injury, stress ligands necessary for their recognition of target cells were also up-regulated in hepatocytes following BDL. Compared to sham-operated wt mice, BDL mice displayed a 13-fold increase in terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and an 11-fold increase in caspase 3/7-positive hepatocytes (P < 0.01). The number of TUNEL and caspase 3/7-positive cells was reduced by > 80% in BDL TRAIL knockout animals (P < 0.05). Likewise, liver histology, number of bile infarcts, serum ALT values, hepatic fibrosis, and animal survival were also improved in BDL TRAIL-/- animals as compared to wt animals. Conclusion: These observations support a pivotal role for TRAIL in cholestatic liver injury mediated by NK 1.1-positive NK/NKT cells.

UR - http://www.scopus.com/inward/record.url?scp=42249091320&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=42249091320&partnerID=8YFLogxK

U2 - 10.1002/hep.22136

DO - 10.1002/hep.22136

M3 - Article

C2 - 18220275

AN - SCOPUS:42249091320

VL - 47

SP - 1317

EP - 1330

JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 4

ER -