Hyperthermia, inducing pancreatic heat-shock proteins, fails to prevent cerulein-induced stress kinase activation

The dually phosphorylated c-jun kinase and p38 mitogen-activated protein (M AP) kinase, also termed stress kinases, are members of the MAP kinase famil y. They are activated early during cerulein pancreatitis induction and have been proposed as regulators during pancreatitis development by us and othe rs. We recently showed that hyperthermia preconditioning induces expression of pancreatic heat-shock proteins (HSP) and protects against cerulein panc reatitis. Because it was further reported that HSP70 can prevent activation of stress kinases in lymphoid tumor cells, we investigated whether hyperth ermia preconditioning might reduce hyperstimulation-mediated activation of pancreatic stress kinases. Pancreatic HSP expression was induced by whole-b ody hyperthermia pre-conditioning. Without prior HSP induction, cerulein le d to a rapid and dose-dependent increase in serum lipase and amylase levels , pancreatic wet weight through edema formation, and activation of pancreat ic MAP kinases. Hyperthermia preconditioning, although strongly inducing HS P70 and almost completely preventing edema formation, as well as the increa se of serum amylase and lipase, did not reduce cerulein-mediated stress kin ase activation. This indicates that in the pancreas, cerulein can strongly activate MAP kinases even when pancreatitis development is greatly inhibite d, and that pancreatic HSPs do not inhibit activation of pancreatic stress kinases in vivo.