title: Thermal stress-induced HSP70 mediates protection against intrapancreatic trypsinogen activation and acute pancreatitis in rats.
abstract: OBJECTIVE
  Prior thermal stress induces heat shock protein 70 (HSP70) expression in the pancreas and protects against secretagogue-induced pancreatitis, but it is not clear that this thermal stress-induced protection is actually mediated by HSP70 since thermal stress may have other, non-HSP related, effects.
  
  
  METHODS
  In the present study, we have administered antisense (AS) oligonucleotides, which prevent pancreatic expression of HSP70 to rats, in vivo, to evaluate this issue. In a separate series of experiments, designed to examine the role of pancreatitis-induced HSP70 expression in modulating the severity of pancreatitis, rats not subjected to prior thermal stress were given AS-HSP70 before cerulein administration, and trypsinogen activation as well as the severity of pancreatitis were evaluated.
  
  
  RESULTS
  Hyperthermia induced HSP70 expression, prevented intrapancreatic trypsinogen activation, and protected against cerulein-induced pancreatitis. Administration of AS-HSP70 but not sense-HSP70 reduced the thermal stress-induced HSP70 expression, restored the ability of supramaximal cerulein stimulation to cause intrapancreatic trypsinogen activation, and abolished the protective effect of prior thermal stress against pancreatitis. In non-thermally stressed animals, pretreatment with AS-HSP70 before the induction of pancreatitis exacerbated all the parameters associated with pancreatitis.
  
  
  CONCLUSIONS
  These findings lead us to conclude that HSP70 induction, rather than some other thermal stress-related phenomenon, mediates the thermal stress-induced protection against pancreatitis and that it protects against pancreatitis by preventing intrapancreatic activation of trypsinogen. The worsening of pancreatitis, which occurs when non-thermally stressed animals are given AS-HSP70 before cerulein, suggests that cerulein-induced HSP70 expression in nontreated animals acts to limit the severity of pancreatitis.
authors.affiliation: Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Bhagat
authors.forename: Vijay P
authors.initials: VP
authors.lastname: Singh
authors.forename: Albert M
authors.initials: AM
authors.lastname: Song
authors.forename: Gijs J D
authors.initials: GJ
authors.lastname: van Acker
authors.forename: Sudhir
authors.initials: S
authors.lastname: Agrawal
authors.forename: Michael L
authors.initials: ML
authors.lastname: Steer
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Saluja
mesh_terms: D000208:Acute Disease; D000818:Animals; D002108:Ceruletide; D005786:Gene Expression Regulation / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D018882:Heat Stress Disorders / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000378:metabolism; D014362:Trypsinogen / Q000378:metabolism*
chemical_list: D018840:HSP70 Heat-Shock Proteins; D016376:Oligonucleotides, Antisense; D002108:Ceruletide; D014362:Trypsinogen