Dilinoleoylphosphatidylcholine decreases acetaldehyde-induced TNF-alpha generation in Kupffer cells of ethanol-fed rats

Biochem Biophys Res Commun. 2002 Dec 6;299(3):459-64. doi: 10.1016/s0006-291x(02)02672-4.

Abstract

We previously reported that dilinoleoylphosphatidylcholine (DLPC) decreases lipopolysaccharide-induced TNF-alpha generation by Kupffer cells of ethanol-fed rats by blocking p38, ERK1/2, and NF-kappaB activation. Here we show that DLPC also decreases TNF-alpha induction by acetaldehyde, a toxic metabolite released by ethanol oxidation. Acetaldehyde induces TNF-alpha generation with a maximal effect at 200 microM and activates p38 and ERK1/2; the latter in turn activates NF-kappaB. This effect is augmented in Kupffer cells of ethanol-fed rats, with upregulation of cytochrome P4502E1 by ethanol. DLPC decreases TNF-alpha generation by blocking p38, ERK1/2, and NF-kappaB activation. Likewise, SB203580, which abolishes p38 activation, and PD098059, which abrogates ERK1/2 and NF-kappaB activation, diminish TNF-alpha generation. Since increased TNF-alpha generation plays a pathogenic role in alcoholic liver disease, the DLPC action on Kupffer cells may explain, in part, its beneficial effects on liver cell injury after ethanol consumption.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetaldehyde / metabolism*
  • Animals
  • Cells, Cultured
  • Cytochrome P-450 CYP2E1 / metabolism
  • Diet
  • Enzyme Inhibitors / pharmacology
  • Ethanol / administration & dosage*
  • Ethanol / metabolism
  • Flavonoids / pharmacology
  • Imidazoles / pharmacology
  • Kupffer Cells / cytology
  • Kupffer Cells / drug effects*
  • Kupffer Cells / metabolism
  • Male
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Phosphatidylcholines / metabolism
  • Phosphatidylcholines / pharmacology*
  • Pyridines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor-alpha / metabolism*
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Enzyme Inhibitors
  • Flavonoids
  • Imidazoles
  • NF-kappa B
  • Phosphatidylcholines
  • Pyridines
  • Tumor Necrosis Factor-alpha
  • Ethanol
  • 1,2-linoleoylphosphatidylcholine
  • Cytochrome P-450 CYP2E1
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Acetaldehyde
  • SB 203580
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one