Hyperthermia, Inducing Pancreatic Heat-Shock Proteins, Fails to Prevent Cerulein-Induced Stress Kinase Activation

Abstract

The dually phosphorylated c-jun kinase and p38 mitogen-activated protein (MAP) kinase, also termed stress kinases, are members of the MAP kinase family. They are activated early during cerulein pancreatitis induction and have been proposed as regulators during pancreatitis development by us and others. We recently showed that hyperthermi preconditioning induces expression of pancreatic heat-shock proteins (HSP) and protects against cerulein pancreatitis. Because it was further reported that HSP70 can prevent activation of stress kinases in lymphoid tumor cells, we investigated whether hyperthermi preconditioning might reduce hyperstimulation-mediated activation of pancreatic stress kinases. Pancreatic HSP expression was induced by whole-body hyperthermi pre-conditioning. Without prior HSP induction, cerulein led to rapid and dose-dependent increase in serum lipase and amylase levels, pancreatic wet weight through edem formation, and activation of pancreatic MAP kinases. Hyperthermi preconditioning, although strongly inducing HSP70 and almost completely preventing edem formation, as well as the increase of serum amylase and lipase, did not reduce cerulein-mediated stress kinase activation. This indicates that in the pancreas, cerulein can strongly activate MAP kinases even when pancreatitis development is greatly inhibited, and that pancreatic HSPs do not inhibit activation of pancreatic stress kinases in vivo.