Hsp72 overexpression accelerates the recovery from acute pancreatitis

Background and aims: 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. Recent data suggest that increased Hsp72 levels may protect 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 β-actin promoter were subjected to seven hourly injections with caerulein. Hsp72 expression and localization was analyzed with real time RT-PCR, Western blotting and immunohistochemistry. The severity of experimental pancreatitis was determined via serum lipase levels as well as pathomorphological evaluation.

Results: Pancreata of untreated Hsp72 mice displayed˜100 x elevated Hsp72 mRNA/protein levels with the immunohistochemical signal localizing predominantly to the exocrine part of the organ. During the course of pancreatitis, Hsp72 levels remained largely unaltered in Hsp72 mice, while a moderate increase (<5 x) was noted in non-transgenic animals. Hsp72 mice displayed only minimal protection from the acute pancreatic injury (slightly lower edema/leukocyte infiltration 6–12h after caerulein injection), but recovered significantly faster (lower lipase levels, edema as well as necrosis score 36h post caerulein) than the nontransgenic animals.

Conclusions: Our data suggest that Hsp72 overexpression accelerates the recovery from acute pancreatitis and may represent a viable treatment strategy.