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Acute pancreatitis induces FasL gene expression and apoptosis in the liver.

Publication ,  Conference
Gallagher, SF; Yang, J; Baksh, K; Haines, K; Carpenter, H; Epling-Burnette, PK; Peng, Y; Norman, J; Murr, MM
Published in: J Surg Res
December 2004

BACKGROUND: Liver injury is an important prognostic indicator in acute pancreatitis. We previously demonstrated that Kupffer cell-derived cytokines mediate liver injury. In this work, we sought to characterize the role of Fas Ligand (FasL) in liver injury during acute pancreatitis. METHODS: Acute pancreatitis was induced in mice using cerulein; serum FasL, AST, ALT, liver FasL, p38-MAPK, and caspase-3 were measured. FasL mRNA and protein and its receptor (Fas) were determined in rat Kupffer cells treated with elastase (1 U/ml) to mimic acute pancreatitis. Apoptosis was measured by flow cytometry. RESULTS: Cerulein-induced pancreatitis increased serum AST, ALT, and FasL and up-regulated liver FasL (1315 +/- 111 versus 310 +/- 164 pg/ml, P = 0.002 versus sham), while inducing p38-MAPK phosphorylation (P < 0.01 versus sham) and cleavage of caspase-3 (P < 0.04 versus sham); all were attenuated by pretreatment with the Kupffer cell inhibitor, gadolinium (all P < 0.003). In vitro, elastase induced a time-dependent increase in Kupffer cell FasL protein (FasL = 404 +/- 94 versus 170 +/- 40, P = 0.02, versus control), a 100-fold increase in FasL mRNA, and up-regulated Fas (FasL receptor). Gadolinium significantly attenuated the elastase-induced increase in FasL and FasL mRNA (FasL = 230 +/- 20 versus 404 +/- 94, P = 0.01, versus elastase) but had little effect on Fas. Additionally, elastase-primed Kupffer cell media induced apoptosis in hepatocytes (29 +/- 1 versus 16% +/- 1%; versus control, P < 0.001). CONCLUSIONS: Acute pancreatitis induces liver injury and hepatocyte death while up-regulating FasL, p38-MAPK, and caspase-3. Fas is up-regulated within Kupffer cells, suggesting that FasL may autoregulate its production by inducing its originator-cell death. The ability to manipulate interactions between Kupffer cells and hepatocytes may have important therapeutic implications.

Duke Scholars

Published In

J Surg Res

DOI

ISSN

0022-4804

Publication Date

December 2004

Volume

122

Issue

2

Start / End Page

201 / 209

Location

United States

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • fas Receptor
  • Up-Regulation
  • Surgery
  • Receptors, Tumor Necrosis Factor
  • Rats, Sprague-Dawley
  • Rats
  • Pancreatitis
  • Mice
  • Membrane Glycoproteins
 

Citation

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Gallagher, S. F., Yang, J., Baksh, K., Haines, K., Carpenter, H., Epling-Burnette, P. K., … Murr, M. M. (2004). Acute pancreatitis induces FasL gene expression and apoptosis in the liver. In J Surg Res (Vol. 122, pp. 201–209). United States. https://doi.org/10.1016/j.jss.2004.05.019
Gallagher, Scott F., Jun Yang, Kathryn Baksh, Krista Haines, Heather Carpenter, P. K. Epling-Burnette, Yanhua Peng, James Norman, and Michel M. Murr. “Acute pancreatitis induces FasL gene expression and apoptosis in the liver.” In J Surg Res, 122:201–9, 2004. https://doi.org/10.1016/j.jss.2004.05.019.
Gallagher SF, Yang J, Baksh K, Haines K, Carpenter H, Epling-Burnette PK, et al. Acute pancreatitis induces FasL gene expression and apoptosis in the liver. In: J Surg Res. 2004. p. 201–9.
Gallagher, Scott F., et al. “Acute pancreatitis induces FasL gene expression and apoptosis in the liver.J Surg Res, vol. 122, no. 2, 2004, pp. 201–09. Pubmed, doi:10.1016/j.jss.2004.05.019.
Gallagher SF, Yang J, Baksh K, Haines K, Carpenter H, Epling-Burnette PK, Peng Y, Norman J, Murr MM. Acute pancreatitis induces FasL gene expression and apoptosis in the liver. J Surg Res. 2004. p. 201–209.
Journal cover image

Published In

J Surg Res

DOI

ISSN

0022-4804

Publication Date

December 2004

Volume

122

Issue

2

Start / End Page

201 / 209

Location

United States

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • fas Receptor
  • Up-Regulation
  • Surgery
  • Receptors, Tumor Necrosis Factor
  • Rats, Sprague-Dawley
  • Rats
  • Pancreatitis
  • Mice
  • Membrane Glycoproteins