title: New insights into the pathogenesis of pancreatitis.
abstract: OBJECTIVE
  In this article, we review important advances in our understanding of the mechanisms of pancreatitis.
  
  
  RESULTS
  The relative contributions of intrapancreatic trypsinogen activation and nuclear factor kappa B (NFκB) activation, the two major early independent cellular events in pancreatitis, have been investigated using novel genetic models. Trypsinogen activation has traditionally held the spotlight for many decades as the central pathogenic event of pancreatitis. However, recent experimental evidence points to the role of trypsin activation in early acinar cell damage but not in the inflammatory response of acute pancreatitis, which was shown to be induced by NFκB activation. Further, chronic pancreatitis developed independently of trypsinogen activation in the caerulein model. Sustained NFκB activation, but not persistent intra-acinar expression of active trypsin, was shown to result in chronic pancreatitis. Calcineurin-NFAT (nuclear factor of activated T-cells) signaling was shown to mediate downstream effects of pathologic rise in intracellular calcium. Interleukin-6 was identified as a key cytokine mediating pancreatitis-associated lung injury.
  
  
  CONCLUSIONS
  Recent advances challenge the long-believed trypsin-centered understanding of pancreatitis. It is becoming increasingly clear that activation of intense inflammatory signaling mechanisms in acinar cells is crucial to the pathogenesis of pancreatitis, which may explain the strong systemic inflammatory response in pancreatitis.
authors.affiliation: Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Raghuwansh P
authors.initials: RP
authors.lastname: Sah
authors.forename: Rajinder K
authors.initials: RK
authors.lastname: Dawra
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Saluja
mesh_terms: D000208:Acute Disease; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D010195:Pancreatitis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D050500:Pancreatitis, Chronic / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology / Q000503:physiopathology; D014357:Trypsin / Q000502:physiology; D014362:Trypsinogen / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D014362:Trypsinogen; D014357:Trypsin
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