| Nuclear factor-kappaB mediates Kupffer cell apoptosis through transcriptional activation of Fas/FasL. | |
| | |
MedLine Citation:
|
PMID: 16154149 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
INTRODUCTION: Nuclear factor (NF)-kappaB is a key transcriptional factor for cell survival, inflammation, and stress response. We demonstrated that Kupffer cell-derived FasL plays a central role in pancreatitis-induced hepatocyte injury. The aim of this study was to determine the role of NF-kappaB in regulating death ligand/receptor pathway in Kupffer cells during conditions that mimic acute pancreatitis. MATERIALS AND METHODS: Tissue cultures of rat Kupffer cells were treated with elastase (1 U/L) to mimic pancreatitis before and after infection with AdIkappaB to block activation of NF-kappaB. Tumor necrosis factor (enzyme-linked immunoassay), Fas/FasL, and caspase-3 (Western), tumor necrosis factor and Fas/FasL mRNA (reverse-transcription polymerase chain reaction), and NF-kappaB DNA binding (electrophoretic mobility shift assay) were determined. Apoptosis was measured by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) and DNA fragmentation. Gels were quantified by densitometry. Data (n=3) are mean+/-SEM; student's t test was used for statistical analysis. RESULTS: AdIkappaB infection up-regulated mutated IkappaBalpha that maintained its binding properties to NF-kappaB. Promoter-reporter assay demonstrated that FasL gene promoter was regulated by NF-kappaB. Infection with AdIkappaB attenuated the elastase-induced up-regulation of Fas/FasL (all P<0.01 versus elastase) and NF-kappaB DNA binding but did not affect elastase-induced up-regulation of TNF. AdIkappaB attenuated elastase-induced cleavage of caspase-3, DNA fragmentation and TUNEL staining (all P<0.01 versus elastase). CONCLUSIONS: Inhibition of NF-kappaB DNA binding down-regulates Fas/FasL and attenuates elastase-induced apoptosis; however, it has no effect on TNF production, suggesting that regulation of Fas/FasL and TNF may occur via different pathways. The ability of Kupffer cells to autoregulate their stress response by up-regulating their death ligand/receptor and apoptosis warrants further investigation. |
| | |
Authors:
|
Yanhua Peng; Scott F Gallagher; Krista Haines; Kathryn Baksh; Michel M Murr |
Related Documents
:
|
12837039 - Characterization of adapt33, a stress-inducible riboregulator. 11641789 - Alterations of fas (apo-1/cd 95) gene and its relationship with p53 in non small cell l... 10652249 - Down-regulation of the endoplasmic reticulum chaperone grp78/bip by vomitoxin (deoxyniv... 10049059 - Fas ligand expression in the bone marrow in myelodysplastic syndromes correlates with f... 15081259 - Dopamine receptor d3 mrna expression in human lymphocytes is negatively correlated with... 11747759 - Mifepristone regulates expression of apoptosis related genes fas and fasl in mouse endo... 15147869 - Involvement of gsk-3beta in tweak-mediated nf-kappab activation. 22300949 - Clinicopathological significance of non-small cell lung cancer with high prevalence of ... 16916039 - Polychlorinated biphenyl load, aryl hydrocarbon receptor, and cytochrome p4501a1 induct... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2005-09-08 |
Journal Detail:
|
Title: The Journal of surgical research Volume: 130 ISSN: 0022-4804 ISO Abbreviation: J. Surg. Res. Publication Date: 2006 Jan |
Date Detail:
|
Created Date: 2006-01-03 Completed Date: 2006-02-15 Revised Date: 2008-11-21 |
Medline Journal Info:
|
Nlm Unique ID: 0376340 Medline TA: J Surg Res Country: United States |
Other Details:
|
Languages: eng Pagination: 58-65 Citation Subset: IM |
Affiliation:
|
Department of Surgery, James A. Haley Veterans Affairs Medical Center, and University of South Florida Health Sciences Center, Tampa, Florida 33601, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Acute Disease Adenoviridae / genetics Animals Antigens, CD95 / genetics* Apoptosis / drug effects, physiology Caspase 3 Caspases / metabolism Cell Line, Transformed Cytomegalovirus / genetics Fas Ligand Protein I-kappa B Proteins / genetics, metabolism Kupffer Cells / cytology*, metabolism* Male Membrane Glycoproteins / genetics* Mutagenesis NF-kappa B / metabolism* Pancreatic Elastase / pharmacology Pancreatitis / metabolism, physiopathology Promoter Regions, Genetic / genetics Rats Rats, Sprague-Dawley Transcriptional Activation / drug effects, physiology Tumor Necrosis Factor-alpha / genetics Tumor Necrosis Factors / genetics* Up-Regulation / drug effects, genetics |
| Grant Support | |
ID/Acronym/Agency:
|
R24 AA12885/AA/NIAAA NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Antigens, CD95; 0/Fas Ligand Protein; 0/I-kappa B Proteins; 0/Membrane Glycoproteins; 0/NF-kappa B; 0/Tnfsf6 protein, rat; 0/Tumor Necrosis Factor-alpha; 0/Tumor Necrosis Factors; 139874-52-5/NF-kappaB inhibitor alpha; EC 3.4.21.36/Pancreatic Elastase; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: In vivo testing of an infection-resistant annuloplasty ring.
Next Document: The effect of amrinone on liver regeneration in experimental hepatic resection model.