Gastroenterology
Volume 141, Issue 6 , Pages 1972-1975 , December 2011

Digesting New Information About the Role of Trypsin in Pancreatitis

  • Baoan Ji
    • ,
  • Craig D. Logsdon

      Affiliations

    • Corresponding Author InformationReprint requests Address requests for reprints to: Craig D. Logsdon, PhD, Distinguished Endowed Professor for Pancreatic Cancer Research, Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Box 953, 1515 Holcombe Blvd, Houston, Texas 77030

References 

  1. Chiari H. Über die Selbstverdauung des menschlichen Pankreas. Zeitschrift für Heilkunde. 1896;17:69–96
  2. Geokas MC, Rinderknecht H. Free proteolytic enzymes in pancreatic juice of patients with acute pancreatitis. Am J Dig Dis. 1974;19:591–598
  3. Steer ML. Search for the trigger mechanism of pancreatitis. Gastroenterology. 1984;86:764–766
  4. Gaisano HY, Gorelick FS. New insights into the mechanisms of pancreatitis. Gastroenterology. 2009;136:2040–2044
  5. Van Acker GJ, Saluja AK, Bhagat L, et al. Cathepsin B inhibition prevents trypsinogen activation and reduces pancreatitis severity. Am J physiol Gastrointest Liver Physiol. 2002;283:G794–G800
  6. Whitcomb DC, Gorry MC, Preston RA, et al. Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene. Nat Genet. 1996;14:141–145
  7. Witt H, Luck W, Hennies HC, et al. Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis. Nat Genet. 2000;25:213–216
  8. Nathan JD, Romac J, Peng RY, et al. Transgenic expression of pancreatic secretory trypsin inhibitor-I ameliorates secretagogue-induced pancreatitis in mice. Gastroenterology. 2005;128:717–727
  9. Halangk W, Lerch MM, Brandt-Nedelev B, et al. Role of cathepsin B in intracellular trypsinogen activation and the onset of acute pancreatitis. J Clin Invest. 2000;106:773–781
  10. Han B, Ji B, Logsdon CD. CCK independently activates intracellular trypsinogen and NF-kappaB in rat pancreatic acinar cells. Am J Physiol Cell Physiol. 2001;280:C465–C472
  11. Halangk W, Kruger B, Ruthenburger M, et al. Trypsin activity is not involved in premature, intrapancreatic trypsinogen activation. Am J Physiol Gastrointest Liver Physiol. 2002;282:G367–G374
  12. Kereszturi E, Szmola R, Kukor Z, et al. Hereditary pancreatitis caused by mutation-induced misfolding of human cationic trypsinogen: a novel disease mechanism. Hum Mutat. 2009;30:575–582
  13. Singh VP, Chari ST. Protease inhibitors in acute pancreatitis: lessons from the bench and failed clinical trials. Gastroenterology. 2005;128:2172–2174
  14. Dawra R, Sah RP, Dudeja V, et al. Intra-acinar trypsinogen activation mediates early stages of pancreatic injury but not inflammation in mice with acute pancreatitis. Gastroenterology. 2011;141:2210–2217
  15. Ji B, Gaiser S, Chen X, et al. Intracellular trypsin induces pancreatic acinar cell death but not NF-kappaB activation. J Biol Chem. 2009;284:17488–17498
  16. Kereszturi E, Sahin-Toth M. Intracellular autoactivation of human cationic trypsinogen mutants causes reduced trypsinogen secretion and acinar cell death. J Biol Chem. 2009;284:33392–33399
  17. Gaiser S, Daniluk J, Liu Y, et al. Intracellular activation of trypsinogen in transgenic mice induces acute but not chronic pancreatitis. Gut. 2011;60:1379–1388
  18. Han B, Logsdon CD. Cholecystokinin induction of mob-1 chemokine expression in pancreatic acinar cells requires NF-kappaB activation. Am J Physiol. 1999;277:C74–C82
  19. Ji B, Chen XQ, Misek DE, et al. Pancreatic gene expression during the initiation of acute pancreatitis: identification of EGR-1 as a key regulator. Physiol Genomics. 2003;14:59–72
  20. Chen X, Ji B, Han B, et al. NF-kappaB activation in pancreas induces pancreatic and systemic inflammatory response. Gastroenterology. 2002;122:448–457
  21. Ji B, Tsou L, Wang H, et al. Ras activity levels control the development of pancreatic diseases. Gastroenterology. 2009;137:1072–1082

 Conflicts of interest The authors disclose no conflicts.

PII: S0016-5085(11)01464-8

doi: 10.1053/j.gastro.2011.10.021

Gastroenterology
Volume 141, Issue 6 , Pages 1972-1975 , December 2011

Article Tools

* Image Usage & Resolution