Skip to main content
Journal cover image

Nuclear factor-kappaB mediates Kupffer cell apoptosis through transcriptional activation of Fas/FasL.

Publication ,  Conference
Peng, Y; Gallagher, SF; Haines, K; Baksh, K; Murr, MM
Published in: J Surg Res
January 2006

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.

Duke Scholars

Published In

J Surg Res

DOI

ISSN

0022-4804

Publication Date

January 2006

Volume

130

Issue

1

Start / End Page

58 / 65

Location

United States

Related Subject Headings

  • fas Receptor
  • Up-Regulation
  • Tumor Necrosis Factors
  • Tumor Necrosis Factor-alpha
  • Transcriptional Activation
  • Surgery
  • Rats, Sprague-Dawley
  • Rats
  • Promoter Regions, Genetic
  • Pancreatitis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Peng, Y., Gallagher, S. F., Haines, K., Baksh, K., & Murr, M. M. (2006). Nuclear factor-kappaB mediates Kupffer cell apoptosis through transcriptional activation of Fas/FasL. In J Surg Res (Vol. 130, pp. 58–65). United States. https://doi.org/10.1016/j.jss.2005.07.030
Peng, Yanhua, Scott F. Gallagher, Krista Haines, Kathryn Baksh, and Michel M. Murr. “Nuclear factor-kappaB mediates Kupffer cell apoptosis through transcriptional activation of Fas/FasL.” In J Surg Res, 130:58–65, 2006. https://doi.org/10.1016/j.jss.2005.07.030.
Peng Y, Gallagher SF, Haines K, Baksh K, Murr MM. Nuclear factor-kappaB mediates Kupffer cell apoptosis through transcriptional activation of Fas/FasL. In: J Surg Res. 2006. p. 58–65.
Peng, Yanhua, et al. “Nuclear factor-kappaB mediates Kupffer cell apoptosis through transcriptional activation of Fas/FasL.J Surg Res, vol. 130, no. 1, 2006, pp. 58–65. Pubmed, doi:10.1016/j.jss.2005.07.030.
Peng Y, Gallagher SF, Haines K, Baksh K, Murr MM. Nuclear factor-kappaB mediates Kupffer cell apoptosis through transcriptional activation of Fas/FasL. J Surg Res. 2006. p. 58–65.
Journal cover image

Published In

J Surg Res

DOI

ISSN

0022-4804

Publication Date

January 2006

Volume

130

Issue

1

Start / End Page

58 / 65

Location

United States

Related Subject Headings

  • fas Receptor
  • Up-Regulation
  • Tumor Necrosis Factors
  • Tumor Necrosis Factor-alpha
  • Transcriptional Activation
  • Surgery
  • Rats, Sprague-Dawley
  • Rats
  • Promoter Regions, Genetic
  • Pancreatitis