Naofen promotes TNF-α-mediated apoptosis of hepatocytes by activating caspase-3 in lipopolysaccharide-treated rats.

World J Gastroenterol

Jun-Hua Fan, Guo-Duo Tang, Hai-Xing Jiang, Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.

Published: May 2014

Aim: To investigate whether naofen is involved in tumor necrosis factor (TNF)-α-mediated apoptosis of hepatocytes induced by lipopolysaccharide (LPS).

Methods: In vivo, rats were treated with LPS or anti-TNF-α antibody, whereas in vitro, primary hepatocytes and Kupffer cells (KCs) were separately isolated from rat livers using collagenase perfusion, and primary hepatocytes were cultured in medium containing LPS or TNF-α, or in conditioned medium from LPS-treated KCs (KC-CM)/KC-CM + anti-TNF-α antibody. Naofen and TNF-α mRNA expression was examined by real-time reverse transcription-polymerase chain reaction. Immunoblotting was used to measure protein expression. Hepatocyte apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay.

Results: LPS significantly induced both naofen expression and caspase-3 activity in the rat liver, which coincided with an increase in the number of TUNEL-positive hepatocytes. The increase of TNF-α expression induced by LPS was preceded by increases in naofen and caspase-3 activity. Elevation of naofen expression and caspase-3 activity was abrogated by pretreatment with anti-TNF-α antibody. In KCs, LPS caused an increase in TNF-α that was almost consistent with that in the liver of LPS-treated rats. In hepatocytes, neither LPS nor TNF-α alone affected either naofen expression or caspase-3 activation. The incubation of hepatocytes with KC-CM significantly enhanced both naofen expression and caspase-3 activity. Moreover, the effects of the KC-CM-induced increase in naofen expression and caspase-3 activity were blocked by anti-TNF-α antibody.

Conclusion: TNF-α released from KCs treated with LPS may induce hepatic naofen expression, which then stimulates hepatocellular apoptosis through activation of caspase-3.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4009528PMC
http://dx.doi.org/10.3748/wjg.v20.i17.4963DOI Listing

Publication Analysis

Top Keywords

naofen expression
24
expression caspase-3
20
caspase-3 activity
20
anti-tnf-α antibody
12
naofen
10
expression
9
tnf-α-mediated apoptosis
8
apoptosis hepatocytes
8
caspase-3
8
treated lps
8

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!