The pancreatic duct epithelium in vitro: bile acid injury and the effect of epidermal growth factor.
BACKGROUND
Pancreatic duct epithelial cells form a barrier against parenchymal injury. The capacity of these cells to respond to injury has not been investigated. We hypothesized that epidermal growth factor (EGF), normally found in pancreatic juice, could protect the duct epithelium from damage.


METHODS
An explant system of duct cell culture developed in our lab with the bovine main pancreatic duct was used. Explants were exposed to bile acid (taurodeoxycholic acid [TDCA] 0, 0.05, 0.5, and 1 mmol/L) in the presence or absence of EGF (0, 1, 10, and 100 nmol/L) for 48 hours. Epithelial proliferation, damage, and growth out from the explant edge were assessed histologically. Expression of ductal markers and the extent of cell proliferation were determined by immunohistochemistry using specific antibodies.


RESULTS
Explant duct cells proliferated and demonstrated continued expression of key duct antigens in culture. TDCA produced dose-dependent mucosal damage and reduced epithelial density and growth from the edge. EGF increased cellular density in the native epithelium, but did not significantly alter growth from the edge. Mucosal damage created by TDCA exposure was significantly decreased with EGF and both growth from the edge and cell density were preserved.


CONCLUSIONS
Explants created from the bovine main pancreatic duct serve as an excellent model for the study of duct epithelial cells in vitro. These cells proliferate in response to EGF and are damaged by TDCA at concentrations below those normally associated with detergent-like activity and below levels observed in bile and duodenal secretions. The ability of EGF to protect from this injury suggests a potential physiologic role in the maintenance of the pancreatic duct mucosal barrier.
Alvarez
C
C
Department of Surgery, University of Maryland, Baltimore, USA.
Nelms
C
C
D'Addio
V
V
Bass
B L
BL
D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000032:analysis; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004848:Epithelium / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D066246:ErbB Receptors / Q000032:analysis; D009092:Mucous Membrane / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D009924:Organ Culture Techniques; D010183:Pancreatic Ducts / Q000166:cytology* / Q000473:pathology / Q000502:physiology; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D013657:Taurodeoxycholic Acid / Q000037:antagonists & inhibitors / Q000633:toxicity*
D018809:Proliferating Cell Nuclear Antigen; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D013657:Taurodeoxycholic Acid; D004815:Epidermal Growth Factor; D066246:ErbB Receptors