Effects of ethanol and its metabolites on human pancreatic stellate cells.
Pancreatic stellate cells (PSCs) play a pivotal role in pancreatic inflammation and fibrosis. In the pancreas, in addition to oxidative metabolism, ethanol can be metabolized by esterification with fatty acids to form fatty acid ethyl esters such as palmitic acid ethyl ester (PAEE). We here examined the effects of ethanol (at 20 or 50 mM), acetaldehyde (at 200 microM), or PAEE (at 100 microM), on PSCs functions. PSCs did not express mRNAs for pancreatic triglyceride lipase and carboxyl ester lipase. Ethanol and acetaldehyde, but not PAEE, induced production of procollagen type I C-peptide. Ethanol, but not acetaldehyde or PAEE, induced interleukin-8 production. PAEE activated activator protein-1, but not nuclear factor kappaB. In addition, PAEE activated extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase. Specific activation of signal transduction pathways and cell functions by ethanol and its metabolites may play a role in alcohol-induced pancreatic injury.
Masamune
Atsushi
A
Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. amasamune@int3.med.tohoku.ac.jp
Satoh
Akihiko
A
Watanabe
Takashi
T
Kikuta
Kazuhiro
K
Satoh
Masahiro
M
Suzuki
Noriaki
N
Satoh
Kennichi
K
Shimosegawa
Tooru
T
D000079:Acetaldehyde / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008049:Lipase / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010168:Palmitates / Q000494:pharmacology; D010179:Pancreas / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011347:Procollagen / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism
D016209:Interleukin-8; D016328:NF-kappa B; D010168:Palmitates; D010446:Peptide Fragments; D011347:Procollagen; D018808:Transcription Factor AP-1; C042813:procollagen type I carboxy terminal peptide; D000431:Ethanol; D003094:Collagen; D020929:Mitogen-Activated Protein Kinase Kinases; C054621:CEL protein, human; D008049:Lipase; D000079:Acetaldehyde