Stellate cell activation in alcoholic pancreatitis.
The pathogenesis of pancreatic fibrosis, a characteristic feature of alcohol-induced chronic pancreatitis, has received increasing attention over the past few years, largely due to the identification and characterization of stellate cells in the pancreas. These cells are morphologically similar to hepatic stellate cells, the principal effector cells in liver fibrosis. The role of pancreatic stellate cells (PSCs) in alcoholic pancreatic fibrosis has been studied using 2 approaches: (i) in vivo studies using pancreatic tissue from patients with alcohol-induced chronic pancreatitis and from animal models of experimental pancreatitis and (ii) in vitro studies using cultured PSCs. These studies indicate that PSCs are activated early in the course of pancreatic injury and are the predominant source of collagen in the fibrotic pancreas. Several factors that may be responsible for mediating PSC activation during chronic alcohol exposure have also been identified. From the findings to date, it may be speculated that the pathogenesis of alcoholic pancreatic fibrosis may involve 2 pathways: (i) a necroinflammatory pathway involving cytokine release and PSC activation and (ii) a nonnecroinflammatory pathway involving direct activation of PSCs by ethanol via its metabolism to acetaldehyde and the generation of oxidant stress.
Apte
M V
MV
Pancreatic Research Group, Department of Gastroenterology, Bankstown-Lidcombe and Liverpool Hospitals and The University of New South Wales, Sydney, Australia. m.apte@unsw.edu.au
Wilson
J S
JS
D000199:Actins / Q000096:biosynthesis; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D000431:Ethanol / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D005355:Fibrosis; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009130:Muscle, Smooth / Q000737:chemistry; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D019512:Pancreatitis, Alcoholic / Q000473:pathology*; D051381:Rats
D000199:Actins; D016207:Cytokines; D016326:Extracellular Matrix Proteins; D000431:Ethanol