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Kupffer cell-derived Fas ligand plays a role in liver injury and hepatocyte death.

Publication ,  Journal Article
Yang, J; Gallagher, SF; Haines, K; Epling-Burnette, PK; Bai, F; Gower, WR; Mastorides, S; Norman, JG; Murr, MM
Published in: J Gastrointest Surg
February 2004

Liver injury is an important prognostic indicator during acute pancreatitis. The aim of this study was to determine the role of Fas ligand (FasL) in hepatocyte injury. Liver parenchymal enzymes were measured in cocultures of hepatocytes and Kupffer cells treated with elastase. FasL and FasL mRNA were measured in elastase-treated Kupffer cells. Hepatocytes were treated with FasL and their viability was assessed by monotetrazolium (MTT), apoptosis by flow cytometry, as well as caspase-3 and p38-mitogen-activated protein kinase (MAPK) by immunoblotting. Elastase increased aspartate aminotransferase and lactate dehydrogenase in cocultures of hepatocyte and Kupffer cells (P<0.040). Elastase increased FasL production from Kupffer cells (P=0.02) and upregulated FasL mRNA (FasL/beta-2 microglobulin (BMG): 0.23+/-0.03 vs. 0.11+/-0.003; P=0.04). FasL increased alanine aminotransferase and lactate dehydrogenase (P<0.03) and reduced hepatocyte viability by 45% (P=0.01). FasL increased the number of dually labeled cells with AnnexinV/7AAD (P=0.03) while upregulating cleavage of caspase-3 and the phosphorylation of p38-MAPK. FasL antibody attenuated the FasL-related increase in dually labeled cells (P=0.02), the cleavage of caspase-3, and phosphorylation of p38-MAPK. Pancreatic elastase upregulates FasL within Kupffer cells. FasL induces hepatocyte injury and death and upregulates p38-MAPK and caspase-3 within hepatocytes. The ability to manipulate interactions between Kupffer cells and hepatocytes may have important therapeutic implications.

Duke Scholars

Published In

J Gastrointest Surg

DOI

ISSN

1091-255X

Publication Date

February 2004

Volume

8

Issue

2

Start / End Page

166 / 174

Location

United States

Related Subject Headings

  • Surgery
  • Rats, Sprague-Dawley
  • Rats
  • Models, Animal
  • Mitogen-Activated Protein Kinases
  • Membrane Glycoproteins
  • Male
  • Liver Diseases
  • Kupffer Cells
  • Hepatocytes
 

Citation

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Yang, J., Gallagher, S. F., Haines, K., Epling-Burnette, P. K., Bai, F., Gower, W. R., … Murr, M. M. (2004). Kupffer cell-derived Fas ligand plays a role in liver injury and hepatocyte death. J Gastrointest Surg, 8(2), 166–174. https://doi.org/10.1016/j.gassur.2003.10.016
Yang, Jun, Scott F. Gallagher, Krista Haines, P. K. Epling-Burnette, Fenqi Bai, William R. Gower, Stephen Mastorides, James G. Norman, and Michel M. Murr. “Kupffer cell-derived Fas ligand plays a role in liver injury and hepatocyte death.J Gastrointest Surg 8, no. 2 (February 2004): 166–74. https://doi.org/10.1016/j.gassur.2003.10.016.
Yang J, Gallagher SF, Haines K, Epling-Burnette PK, Bai F, Gower WR, et al. Kupffer cell-derived Fas ligand plays a role in liver injury and hepatocyte death. J Gastrointest Surg. 2004 Feb;8(2):166–74.
Yang, Jun, et al. “Kupffer cell-derived Fas ligand plays a role in liver injury and hepatocyte death.J Gastrointest Surg, vol. 8, no. 2, Feb. 2004, pp. 166–74. Pubmed, doi:10.1016/j.gassur.2003.10.016.
Yang J, Gallagher SF, Haines K, Epling-Burnette PK, Bai F, Gower WR, Mastorides S, Norman JG, Murr MM. Kupffer cell-derived Fas ligand plays a role in liver injury and hepatocyte death. J Gastrointest Surg. 2004 Feb;8(2):166–174.
Journal cover image

Published In

J Gastrointest Surg

DOI

ISSN

1091-255X

Publication Date

February 2004

Volume

8

Issue

2

Start / End Page

166 / 174

Location

United States

Related Subject Headings

  • Surgery
  • Rats, Sprague-Dawley
  • Rats
  • Models, Animal
  • Mitogen-Activated Protein Kinases
  • Membrane Glycoproteins
  • Male
  • Liver Diseases
  • Kupffer Cells
  • Hepatocytes