Dilinoleoylphosphatidylcholine decreases acetaldehyde-induced TNF-alpha generation in Kupffer cells of ethanol-fed rats.
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.
Cao
Qi
Q
Alcohol Research and Treatment Center, Veterans Affairs Medical Center (151-2), Mount Sinai School of Medicine, 130 West Kingsbridge Road, Bronx, NY 10468, USA.
Mak
Ki M
KM
Lieber
Charles S
CS
D000079:Acetaldehyde / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D004032:Diet; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000008:administration & dosage* / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007728:Kupffer Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D016328:NF-kappa B / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D016328:NF-kappa B; D010713:Phosphatidylcholines; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; C002448:1,2-linoleoylphosphatidylcholine; D019392:Cytochrome P-450 CYP2E1; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000079:Acetaldehyde; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one