Heat shock response is associated with protection against acute interstitial pancreatitis in rats

• Published in: Digestive diseases and sciences 2000-11, Vol.45 (11), p.2252-2264
• Main Authors: WEBER, H, WAGNER, A. C. C, JONAS, L, MERKORD, J, HOFKEN, T, NIZZE, H, LEITZMANN, P, GOKE, B, SCHUFF-WERNER, P
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Ceruletide; Female; Gastroenterology. Liver. Pancreas. Abdomen; Heat-Shock Proteins - metabolism; HSP72 Heat-Shock Proteins; Hyperthermia, Induced; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Organotin Compounds; Other diseases. Semiology; Pancreas - pathology; Pancreatitis, Acute Necrotizing - chemically induced; Pancreatitis, Acute Necrotizing - pathology; Rats; Rats, Inbred Lew; Transforming Growth Factor beta - metabolism
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1023/A:1026459001195

We recently reported that hyperthermia induces pancreatic expression of heat shock proteins (HSPs), particularly HSP70 isoforms, and protects against cerulein pancreatitis. We have now studied whether a double hyperthermia amplifies these effects and whether hyperthermia also protects against dibutyltin dichloride (DBTC)-induced pancreatitis. A further aim was to examine whether hyperthermia induces changes in transforming growth factor-beta1 (TGF-beta1). Following pretreatment without or with a single or double hyperthermia, pancreatitis was induced by application of cerulein or DBTC. Pancreatic HSP and TGF-beta1 expression were studied by immunoblotting. Pancreas injury was assessed by light microscopy and serum pancreatic enzyme activity. Hyperthermia as well as DBTC induced HSP72, whereas cerulein did not. A double hyperthermia led to a further increase in HSP72 compared to a single heat stress. In both models, hyperthermia significantly reduced pancreatic injury. Although a double hyperthermia slightly decreased the severity of cerulein pancreatitis compared to a single heat treatment, an improved pancreas protection against DBTC cytotoxicity was not achieved. We also found that hyperthermia induces the expression of TGF-beta1. In conclusion, hyperthermia preconditioning exerts protective effects against two pathophysiologically different types of pancreatitis by a mechanism that involves the up-regulation of HSP70 isoforms as well as TGF-beta1.