Hsp72 overexpression accelerates the recovery from caerulein-induced pancreatitis.
OBJECTIVE
Heat shock protein (Hsp) 72 is a molecular chaperone which is upregulated in response to a variety of stress situations and has a general cytoprotective function. Increased Hsp72 levels were implicated in protection from acute pancreatitis; a hypothesis which was not tested in a transgenic mouse model yet.


METHODS
To analyze the role of Hsp72 during acute pancreatitis, well-characterized transgenic animals overexpressing rat Hsp72 (Hsp72 mice) under the control of the ß-actin promoter were subjected to caerulein- and L-arginine-induced acute pancreatitis. The severity of experimental pancreatitis was determined via serum lipase levels, morphometric evaluation and quantification of pancreatic edema/inflammation.


RESULTS
Hsp72 mice displayed ∼100-times Hsp72 overexpression, but no changes in the remaining chaperones. Robust Hsp72 signal was observed in pancreatic acini, but not in islets or ductal cells. In both models, elevated Hsp72 did not protect from development of acute pancreatitis and the pancreatitis-associated lung injury, but accelerated recovery from caerulein-induced tissue injury (lower lipase levels, edema, inflammation and necrosis 36 h after caerulein administration). The observed protective function of Hsp72 in caerulein-induced pancreatitis is likely due to an attenuated NF-κB signalling.


CONCLUSIONS
Hsp72 overexpression accelerates the recovery from acute pancreatitis and may represent a potential treatment strategy.
Department of Internal Medicine I, University Medical Center Ulm, Ulm, Germany. Mariia.Lunova@uniklinik-ulm.de
Mariia
M
Lunova
Eugen
E
Zizer
Ozlem
O
Kucukoglu
Carolin
C
Schwarz
Wolfgang H
WH
Dillmann
Martin
M
Wagner
Pavel
P
Strnad
D000208:Acute Disease; D000818:Animals; D001120:Arginine / Q000009:adverse effects; D002108:Ceruletide / Q000009:adverse effects; D004195:Disease Models, Animal; D015870:Gene Expression; D005786:Gene Expression Regulation; D050884:HSP72 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D046790:Pancreas, Exocrine / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D020127:Recovery of Function / Q000235:genetics*; D015398:Signal Transduction
D050884:HSP72 Heat-Shock Proteins; D016328:NF-kappa B; D002108:Ceruletide; D001120:Arginine