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Heat Shock Response is Associated with Protection Against Acute Interstitial Pancreatitis in Rats

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Abstract

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-β1 (TGF-β1). Following pretreatment without or with a single or double hyperthermia, pancreatitis was induced by application of cerulein or DBTC. Pancreatic HSP and TGF-β1 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-β1. 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-β1.

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REFERENCES

  1. Bellmann K, Wenz A, Radons J, Burkart V, Kleemann R, Kolb H: Heat shock induces resistance in rat pancreatic islet cells against nitric oxide, oxygen radicals and streptozotocin toxicity in vitro. J Clin Invest 95:2840–2845, 1995

    Google Scholar 

  2. Craig EA: The heat shock response. CRC Critical Rev Biochem 18:239–280, 1990/1991

    Google Scholar 

  3. Currie RW: Effects of ischemia and perfusion temperature on the synthesis of stress-induced (heat shock) proteins in isolated and perfused rat hearts. J Mol Cell Cardiol 19:795–808, 1987

    Google Scholar 

  4. Donati YR A, Slosman DO, Polla BS: Oxidative injury and the heat shock response. Biochem Pharmacol 40:2571–2577, 1990

    Google Scholar 

  5. Marini M, Frabetti F, Musiani D, Franceschi C: Oxygen radicals induce stress proteins and tolerance to oxidative stress in human lymphocytes. Int J Radiat Biol 70:337–350, 1996

    Google Scholar 

  6. Morimoto RI, Tissieres A, Georgopoulos C (eds). The Biology of Heat Shock Proteins and Molecular Chaperones. Cold Spring Harbor, New York, Cold Spring Harbor Laboratory Press, 1994

    Google Scholar 

  7. Landry J, Bernier D, Chretien P, Nicole LM, Tanguay RM, Marceau N: Synthesis and degradation of heat shock proteins during development and decay of thermotolerance. Cancer Res 42:2457–2461, 1982

    Google Scholar 

  8. Li GC, Werb Z: Correlation between synthesis of heat shock proteins and development of thermotolerance in Chinese hamster fibroblasts. Proc Natl Acad Sci USA 79:3218–3222, 1982

    Google Scholar 

  9. Jäättelä M, Wissing D, Bauer PA, Li GC: Major heat shock protein hsp70 protects tumor cells from tumor necrosis factor cytotoxicity. EMBO J 11:3507–3512, 1992

    Google Scholar 

  10. Nakamura K, Rokutan K, Marni N, Aoike A, Kawai K: Induction of heat shock proteins and their implication in protection against ethanol-induced damage in cultured guinea pig gastric mucosa cells. Gastroenterology 101:161–166, 1991

    Google Scholar 

  11. Spitz DR, Dewey WC, Li GC: Hydrogene peroxide or heat shock induces resistance to hydrogen peroxide in Chinese hamster fibroblasts. J Cell Physiol 131:364–373, 1987

    Google Scholar 

  12. Otaka M, Okuyama A, Otani S, Jin M, Itho S, Itoh H, Iwabuchi A, Sasahara H, Odashima M, Tashima Y, Masamune O: Differential induction of HSP60 and HSP72 by different stress situations in rats. Correlation with cerulein-induced pancreatitis. Dig Dis Sci 42:1473–1479, 1997

    Google Scholar 

  13. Wagner ACC, Weber H, Jonas L, Nizze H, Strowski M, Fiedler F, Printz H, Steffen H, Göke B: Hyperthermia induces heat shock protein expression and protection against cerulein-induced pancreatitis in rats. Gastroenterology 111:1333–1342, 1996

    Google Scholar 

  14. Massagué J: The transforming growth factor-α family. Annu Rev Cell Biol 6:597–641, 1990

    Google Scholar 

  15. Takenaka IM, Hightower LE: Transforming growth factor-α1 rapidly induces Hsp70 and Hsp90 molecular chaperones in cultured chicken embryo cells. J Cell Physiol 152:568–577, 1992

    Google Scholar 

  16. Cao Y, Ohwatari N, Matsumoto T, Kosaka M, Ohtsuru A, Yamashita S: TGF-α1 mediates 70–kDa heat shock protein induction due to ultraviolet irradiation in human skin fibroblasts. Pfluegers Arch Eur J Physiol 438:239–244, 1999

    Google Scholar 

  17. Flanders KC, Winokur TS, Holder MG, Sporn MB: Hyperthermia induces expression of transforming growth factor-αs in rat cardiac cells in vitro and in vivo. J Clin Invest 92:404–410, 1993

    Google Scholar 

  18. Kimmel EC, Fish RH, Casida JE: Bioorganotin chemistry. Metabolism of organotin compounds in microsomal monooxygenase system and in mammals. Agric Food Chem 25:1–9, 1977

    Google Scholar 

  19. Wagner ACC, Wishart MJ, Mulders SM, Blevins PM, Andrews PC, Williams JA: GP-3: A newly characterized protein on the inner surface of the zymogen granule membrane undergoes regulated secretion. J Biol Chem 269:9099–9104, 1994

    Google Scholar 

  20. Gherzi R, Fehmann HC, Volz A, Ponasi M, Göke B: The glucagon gene is transcribed in α-like pancreatic cells. Exp Cell Res 218:460–468, 1995

    Google Scholar 

  21. Sachs L: Angewandte Statistik: Anwendungen statistischer Methoden. Berlin, Springer Verlag, 1992, pp 351–360

    Google Scholar 

  22. Strowski MZ, Sparmann G, Weber H, Fiedler F, Printz H, Jonas L, Göke B, Wagner ACC: Caerulein pancreatitis increases mRNA but reduces protein levels of rat pancreatic heat shock proteins. Am J Physiol 273:G937–G945, 1997

    Google Scholar 

  23. Weber H, Merkord J, Jonas L, Wagner A, Schröder H, Käding U, Werner A, Dummler W: Oxygen radical generation and acute pancreatitis: Effects of dibutyltin dichloride/ethanol and ethanol on rat pancreas. Pancreas 11:382–388, 1995

    Google Scholar 

  24. Merkord J, Jonas L, Weber H, Kröning G, Nizze H, Hennighausen G: Acute interstitial pancreatitis in rats induced by dibutyltin dichloride (DBTC): Pathogenesis and natural course of lesions. Pancreas 15:392–401, 1997

    Google Scholar 

  25. Metzler W, Höfken T, Weber H, Printz H, Göke B, Wagner ACC: Hyperthermia, inducing pancreatic HSP's, failed to prevent cerulein-induced stress kinase activation. Pancreas 19:150–157, 1999

    Google Scholar 

  26. Frossard JL, Saluja A, Lee HS, Bhagat L, Bhatia M, Steer M: Heat shock protein (HSP) 70 expression reduces the severity of caerulein-induced acute pancreatitis by reducing intrapancreatic active trypsin levels. Gastroenterology 114:A330, 1998

    Google Scholar 

  27. Grise K, Kim F, McFadden D: Hyperthermia-induced expression of heat shock protein prevents death in necrotizing pancreatitis. Gastroenterology 114:A334, 1998

    Google Scholar 

  28. Gorelick G, Adler G, Kern HF: Cerulein-induced pancreatitis. In The Pancreas. Biology, Pathobiology and Disease. VLW Go, EP DiMagno, JD Gardner, E Lebenthal, HA Reber, GA Scheele (eds). New York, Raven Press, 1993, pp 501–526

    Google Scholar 

  29. Albers R, van der Pijl A, Bol M, Seinen W, Pieters R: Stress proteins (HSPs) and chemical-induced autoimmunity. Toxicol Appl Pharmacol 140:70–76, 1996

    Google Scholar 

  30. Zhang H, Liu AY-C: Tributyltin is a potent inducer of the heat shock response in human diploid fibroblasts. J Cell Physiol 153:460–466, 1992

    Google Scholar 

  31. Burdon RH, Gill MV, Rice-Evans C: Oxidative stress and heat shock protein induction in human cells. Free Radic Res Commun 3:129–139, 1987

    Google Scholar 

  32. Hartl FU, Hlodan R, Langer T: Molecular chaperones in protein folding: the art of avoiding sticky situations. TIBS 19:20–25, 1994

    Google Scholar 

  33. Benjamin VJ, Horie S, Greenberg ML, Alpern RJ, Williams RS: Induction of stress proteins in cultured myogenic cells. J Clin Invest 89:1685–1689, 1992

    Google Scholar 

  34. Penniks AH, Verschuren PM, Seinen W: Di-n-butyltin dichloride uncouples oxidative phosphorylation in rat liver mitochondria. Toxicol Appl Pharmacol 70:115–120, 1983

    Google Scholar 

  35. Weber H, Roesner JP, Nebe B, Rychly J, Werner A, Schröder H, Jonas L, Leitzmann P, Schneider K-P, Dummler W: Increased cytosolic Ca2+ amplifies oxygen radical-induced alterations of the ultrastructure and the energy metabolism of isolated rat pancreatic acinar cells. Digestion 59:75–185, 1998

    Google Scholar 

  36. Lüthen R, Niederau C, Grendell JH: Intrapancreatic zymogen activation and levels of ATP and glutathione during caerulein pancreatitis in rats. Am J Physiol 268:G595–G602, 1995

    Google Scholar 

  37. Rokutan K, Hirakawa T, Teshima S, Honda S, Kishi K: Glutathione depletion impairs transcripional activation of heat shock genes in primary cultures of guinea pig gastric mucosal cells. J Clin Invest 97:2242–2250, 1996

    Google Scholar 

  38. Rokutan K, Hirakawa T, Teshima S, Nakano Y, Miyoshi M, Kawai T, Konda E, Morinaga H, Nikawa T, Kishi K: Implications of heat shock/stress proteins for medicine and disease. J Med Invest 44:137–147, 1998

    Google Scholar 

  39. Emami J, Schwartz JH, Borkan SC: Transient ischemia or heat stress induces a cytoprotectant protein in rat kidney. Am J Physiol 260:F479–F485, 1991

    Google Scholar 

  40. Adler G, Hupp T, Kern HF: Course and spontaneous regression of acute pancreatitis. Virchows Arch (A) 382:31–47, 1979

    Google Scholar 

  41. Riesle E, Friess H, Zhao L, Wagner M, Uhl W, Baczako K, Gold LI, Korc M, Büchler MW: Increased expression of transforming growth factor bs after acute oedematous pancreatitis in rats suggests a role in pancreatic repair. Gut 40:73–79, 1997

    Google Scholar 

  42. Menke A, Yamaguchi H, Gress TM, Adler G: Extracellular matrix is reduced by inhibiting of transforming growth factor beta 1 in pancreatis in the rat. Gastroenterology 113:295–303, 1997

    Google Scholar 

  43. Konturek PC, Demski A, Warzecha Z, Ihlm A, Ceranowicz P, Konturek SJ, Stachura J, Hahn EG: Comparison of epidermal growth factor and transforming growth factor-beta1 expression in hormone-induced acute pancreatitis in rats. Digestion 59:110–119, 1998

    Google Scholar 

  44. Merkord J, Weber H, Sparmann G, Jonas L, Hennighausen G: The course of pancreatic fibrosis induced by dibutyltin dichloride (DBTC). Ann NY Acad Sci 30:231–237, 1999

    Google Scholar 

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Authors and Affiliations

  1. Institutes of Clinical Chemistry and Pathobiochemistry, Pathology, and Pharmacology and Toxicology, University of Rostock, D-18057, Rostock, Germany

    H. Weber, A.C.C. Wagner, L. Jonas, J. Merkord, T. Hõfken, H. Nizze, P. Leitzmann, B. Gõke & P. Schuff-Werner

  2. Department of Gastroenterology, University of Bern, CH-3010, Bern, Switzerland

    H. Weber, A.C.C. Wagner, L. Jonas, J. Merkord, T. Hõfken, H. Nizze, P. Leitzmann, B. Gõke & P. Schuff-Werner

  3. Department of Pediatrics, Johann Wolfgang Goethe University, D-60590, Frankfurt/Main, Germany

    H. Weber, A.C.C. Wagner, L. Jonas, J. Merkord, T. Hõfken, H. Nizze, P. Leitzmann, B. Gõke & P. Schuff-Werner

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  1. H. Weber
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Weber, H., Wagner, A., Jonas, L. et al. Heat Shock Response is Associated with Protection Against Acute Interstitial Pancreatitis in Rats. Dig Dis Sci 45, 2252–2264 (2000). https://doi.org/10.1023/A:1026459001195

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