PMID- 15353169
OWN - NLM
STAT- MEDLINE
DCOM- 20050211
LR  - 20181130
IS  - 0741-8329 (Print)
IS  - 0741-8329 (Linking)
VI  - 33
IP  - 1
DP  - 2004 May
TI  - Ethanol increases tumor necrosis factor-alpha receptor-1 (TNF-R1) levels in 
      hepatic, intestinal, and cardiac cells.
PG  - 9-15
AB  - Chronic ethanol consumption leads to cell injury in virtually every tissue. Tumor 
      necrosis factor-alpha (TNF-alpha) constitutes a major factor in the development 
      of alcohol-induced liver injury. In alcohol-dependent subjects, elevated levels 
      of plasma TNF-alpha are strongly predictive of mortality. Binding of TNF-alpha to 
      TNF-alpha receptor-1 (TNF-R1) activates death domain pathways, leading to 
      necrosis and apoptosis in most tissues, and it also increases the expression of 
      intercellular adhesion molecules (i.e., ICAM-1), which promote inflammation. We 
      determined whether ethanol exposure leads to increases in cellular TNF-R1. We 
      incubated HepG2 human hepatoma cells and H4-II-E-C3 rat hepatoma cells with 25, 
      50, and 100 mM ethanol for various intervals of time up to 48 h. Human colonic 
      adenocarcinoma cells (Caco-2 cells) and neonatal rat primary cardiomyocytes were 
      also incubated with different concentrations of ethanol. Levels of TNF-R1 were 
      measured either by a sandwich enzyme-linked immunosorbent assay (ELISA) method or 
      by determining the extracellular transmembrane domain of TNF-R1 by an intact-cell 
      ELISA method. Ethanol exposure for 48 h increased TNF-R1 levels in human hepatoma 
      cells in a dose-dependent manner. Levels increased significantly by 164% at 50 mM 
      and by 240% at 100 mM ethanol. Effects were time dependent and did not reach a 
      plateau at 48 h. Similar increases in TNF-R1 were also observed in rat hepatoma 
      cells (90% at 50 mM and 230% at 100 mM ethanol). Under similar conditions, Caco-2 
      cells showed a significant 80% increase in TNF-R1 levels at 200 mM ethanol, a 
      concentration found in intestine. Neonatal rat primary cardiomyocytes showed 
      TNF-R1 increases of 36% at 50 mM and 44% at 100 mM ethanol. These results 
      indicate that exposure of different cell types to pharmacologic concentrations of 
      ethanol increases TNF-R1 levels and may augment TNF-alpha-mediated cell injury in 
      different tissues.
FAU - Rodriguez, Diego A
AU  - Rodriguez DA
AD  - Millennium Institute for Advanced Studies in Cell Biology and Biotechnology, 
      University of Chile, Santiago 6531057, Chile.
FAU - Moncada, Claudio
AU  - Moncada C
FAU - Nunez, Marco T
AU  - Nunez MT
FAU - Lavandero, Sergio
AU  - Lavandero S
FAU - Ponnappa, Biddanda C
AU  - Ponnappa BC
FAU - Israel, Yedy
AU  - Israel Y
LA  - eng
GR  - R01 AA-10967/AA/NIAAA NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Alcohol
JT  - Alcohol (Fayetteville, N.Y.)
JID - 8502311
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 3K9958V90M (Ethanol)
SB  - IM
MH  - Animals
MH  - Caco-2 Cells
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Ethanol/*pharmacology
MH  - Humans
MH  - Intestinal Mucosa/metabolism
MH  - Intestines/cytology/*drug effects
MH  - Liver/cytology/*drug effects/metabolism
MH  - Myocytes, Cardiac/cytology/*drug effects/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Tumor Necrosis Factor, Type I/*biosynthesis
MH  - Up-Regulation/*drug effects
EDAT- 2004/09/09 05:00
MHDA- 2005/02/12 09:00
CRDT- 2004/09/09 05:00
PHST- 2004/01/21 00:00 [received]
PHST- 2004/03/26 00:00 [revised]
PHST- 2004/03/28 00:00 [accepted]
PHST- 2004/09/09 05:00 [pubmed]
PHST- 2005/02/12 09:00 [medline]
PHST- 2004/09/09 05:00 [entrez]
AID - S0741-8329(04)00056-4 [pii]
AID - 10.1016/j.alcohol.2004.03.001 [doi]
PST - ppublish
SO  - Alcohol. 2004 May;33(1):9-15. doi: 10.1016/j.alcohol.2004.03.001.