Caerulein pancreatitis increases mRNA but reduces protein levels of rat pancreatic heat shock proteins

Abstract

We have recently reported that preconditioning through hyperthermia induces expression of pancreatic heat shock proteins (HSPs) and protects against caerulein pancreatitis. Here, we investigate caerulein-mediated effects on pancreatic HSPs without prior hyperthermia. Caerulein time and dose dependently increased pancreatic mRNA levels of the constitutive isoform of HSP70 (HSC70). However, pancreatic HSC70 protein levels were decreased, as were HSP60 protein levels. Also, in contrast to hyperthermia preconditioning, caerulein did not induce measurable levels of mRNA or protein of the inducible isoform of HSP70. Thus the pancreas reacts to different kinds of stress (hyperthermia vs. hyperstimulation) with differential induction of HSP mRNAs. Clearly, hyperthermia leads to induction of HSP protein expression, whereas caerulein treatment does not. Therefore, our current study further supports the idea that hyperthermia-induced protection against caerulein pancreatitis may be mediated through increased protein levels of pancreatic HSPs. It is further tempting to hypothesize that failure to appropriately increase HSP protein levels in response to high doses of caerulein might be a factor in the development of pancreatitis.

The 3-Hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) Reductase Inhibitor, Lovastatin (Statin) Ameliorates CCK-Induced Acute Pancreatitis in Rats

“…4,5) It has been shown that the preinduction of HSP expression has a protective effect against cerulean induced pancreatitis in rats or choline-deficient ethionine-supplemented diet model pancreatitis in mice. 9,10) This observation suggests that the low levels of pancreatic HSPs might be involved in the development of CCK-induced pancreatitis. Rakonczay et al demonstrated that CCK-induced pancreatitis reduces the levels of pancreatic HSPs.…”

“…But Strowski et al demonstrated that caeruleininduced pancreatitis reduces the levels of pancreatic HSPs. 9) And Rakonczay et al also reported that CCK-induced pancreatitis reduces the levels of pancreatic HSPs. 10) Thus, we checked the effect of statin on HSP 60 expression in acute pancreatitis.…”

“…But caerulein or CCK-induced pancreatitis reduces the levels of pancreatic HSPs. 9,10) Cytokines are important immunoregulatory mediators. Their contribution to the pathogenesis of acute and chronic gastroenterological disorders is obvious.…”

Effect of hyperthermia on experimental acute pancreatitis

“…Another suggestion is that hyperthermia might directly prevent the activation of pancreatic enzymes; however, another report showed that kinase activation activity was unaltered after heating procedure (24) ; nevertheless, this issue is controversial and other studies had demonstrated opposite results (4,13) . Another explanation is that the protective effect afforded by hyperthermia could be mediated by HSPs ("heat shock proteins") (35,37) . It is believed that HSPs act as molecular chaperones, making the fi nal folding of other proteins easier and protecting them from additional injuries.…”

Efficacy of tocilizumab treatment in cerulein-induced experimental acute pancreatitis model in rats

“…The effect of cerulein is dependent on dose and frequency. The dose and duration of administration are determined according to the required pancreatitis severity (12,13). It has been shown that the administration of cerulein subcutaneously at the dose of 10-20 μg/kg causes acute edematous pancreatitis (14,15).…”