PMID- 15797225
OWN - NLM
STAT- MEDLINE
DCOM- 20050901
LR  - 20181113
IS  - 1091-255X (Print)
IS  - 1091-255X (Linking)
VI  - 9
IP  - 4
DP  - 2005 Apr
TI  - Fas/FasL play a central role in pancreatitis-induced hepatocyte apoptosis.
PG  - 467-74; discussion 474-5
AB  - 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.
FAU - Gallagher, Scott F
AU  - Gallagher SF
AD  - Departments of Surgery, James A. Haley Veterans Affairs Medical Center, 
      University of South Florida Health Sciences Center, Tampa, Florida, USA.
FAU - Peng, Yanhua
AU  - Peng Y
FAU - Haines, Krista
AU  - Haines K
FAU - Baksh, Kathryn
AU  - Baksh K
FAU - Epling-Burnette, P K
AU  - Epling-Burnette PK
FAU - Yang, Jun
AU  - Yang J
FAU - Murr, Michel M
AU  - Murr MM
LA  - eng
GR  - R24 AA12885/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - J Gastrointest Surg
JT  - Journal of gastrointestinal surgery : official journal of the Society for Surgery 
      of the Alimentary Tract
JID - 9706084
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Fas protein, mouse)
RN  - 0 (Fasl protein, mouse)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (fas Receptor)
RN  - 9007-43-6 (Cytochromes c)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - *Apoptosis
MH  - Blotting, Western
MH  - Cytochromes c/metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Fas Ligand Protein
MH  - Female
MH  - Hepatocytes/*metabolism
MH  - In Situ Nick-End Labeling
MH  - Kupffer Cells/metabolism
MH  - Membrane Glycoproteins/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Pancreatitis/metabolism/*physiopathology
MH  - Receptors, Tumor Necrosis Factor/*metabolism
MH  - Up-Regulation
MH  - fas Receptor
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2005/03/31 09:00
MHDA- 2005/09/02 09:00
CRDT- 2005/03/31 09:00
PHST- 2005/03/31 09:00 [pubmed]
PHST- 2005/09/02 09:00 [medline]
PHST- 2005/03/31 09:00 [entrez]
AID - S1091-255X(04)00588-8 [pii]
AID - 10.1016/j.gassur.2004.12.008 [doi]
PST - ppublish
SO  - J Gastrointest Surg. 2005 Apr;9(4):467-74; discussion 474-5. doi: 
      10.1016/j.gassur.2004.12.008.