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Fas/FasL play a central role in pancreatitis-induced hepatocyte apoptosis.

Publication ,  Journal Article
Gallagher, SF; Peng, Y; Haines, K; Baksh, K; Epling-Burnette, PK; Yang, J; Murr, MM
Published in: J Gastrointest Surg
April 2005

Liver injury is a clinical prognostic indicator in acute pancreatitis (AP). We have demonstrated that Kupffer cell-derived FasL mediates liver injury during AP and sought to determine its role in AP-induced hepatocyte apoptosis. AP was induced in National Institutes of Health (NIH) Swiss mice, C57/C57, and Fas-/-, FasL-/- mice by a choline-deficient ethionine-supplement diet. Liver Fas, FasL, p38-mitogen activated phosphokinase (p38-MAPK), poly-ADP ribose polymerase (PARP), and cytochrome C were measured by immunoblotting. Apoptosis was assessed by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) and DNA fragmentation (ELISA). AP upregulated liver FasL (4280 +/- 580 vs. 733 +/- 336), Fas (2866 +/- 595 vs. 649 +/- 111), cytochrome C (6980 +/- 237 vs. 903 +/- 156), and PARP (6393 +/- 591 vs. 466 +/- 261) as well as increased TUNEL staining (40 +/- 2 vs. 14 +/- 1) and DNA fragmentation (all P < 0.03 vs. control). In FasL-/- and Fas-/- mice, AP-induced upregulation of p38-MAPK, PARP, and cytochrome C was significantly attenuated (all P < 0.01 compared to C57/C57 control). In addition, AP-induced DNA fragmentation was reduced 60% in Fas-/- and FasL-/- mice (P < 0.01 vs. C57/C57). AP induces apoptosis by transcriptional activation of Fas/FasL. AP-induced apoptosis was significantly reduced in Fas and FasL knockout mice along with downregulation of p38-MAPK, PARP, and cytochrome C, thereby suggesting a central role for Fas/FasL in hepatocyte apoptosis. The manipulation of interactions between Kupffer cell-derived FasL and hepatocytes may have important therapeutic implications.

Duke Scholars

Published In

J Gastrointest Surg

DOI

ISSN

1091-255X

Publication Date

April 2005

Volume

9

Issue

4

Start / End Page

467 / 474

Location

United States

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • fas Receptor
  • Up-Regulation
  • Surgery
  • Receptors, Tumor Necrosis Factor
  • Pancreatitis
  • Mice, Inbred C57BL
  • Mice
  • Membrane Glycoproteins
  • Kupffer Cells
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Gallagher, S. F., Peng, Y., Haines, K., Baksh, K., Epling-Burnette, P. K., Yang, J., & Murr, M. M. (2005). Fas/FasL play a central role in pancreatitis-induced hepatocyte apoptosis. J Gastrointest Surg, 9(4), 467–474. https://doi.org/10.1016/j.gassur.2004.12.008
Gallagher, Scott F., Yanhua Peng, Krista Haines, Kathryn Baksh, P. K. Epling-Burnette, Jun Yang, and Michel M. Murr. “Fas/FasL play a central role in pancreatitis-induced hepatocyte apoptosis.J Gastrointest Surg 9, no. 4 (April 2005): 467–74. https://doi.org/10.1016/j.gassur.2004.12.008.
Gallagher SF, Peng Y, Haines K, Baksh K, Epling-Burnette PK, Yang J, et al. Fas/FasL play a central role in pancreatitis-induced hepatocyte apoptosis. J Gastrointest Surg. 2005 Apr;9(4):467–74.
Gallagher, Scott F., et al. “Fas/FasL play a central role in pancreatitis-induced hepatocyte apoptosis.J Gastrointest Surg, vol. 9, no. 4, Apr. 2005, pp. 467–74. Pubmed, doi:10.1016/j.gassur.2004.12.008.
Gallagher SF, Peng Y, Haines K, Baksh K, Epling-Burnette PK, Yang J, Murr MM. Fas/FasL play a central role in pancreatitis-induced hepatocyte apoptosis. J Gastrointest Surg. 2005 Apr;9(4):467–474.
Journal cover image

Published In

J Gastrointest Surg

DOI

ISSN

1091-255X

Publication Date

April 2005

Volume

9

Issue

4

Start / End Page

467 / 474

Location

United States

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • fas Receptor
  • Up-Regulation
  • Surgery
  • Receptors, Tumor Necrosis Factor
  • Pancreatitis
  • Mice, Inbred C57BL
  • Mice
  • Membrane Glycoproteins
  • Kupffer Cells