New insights into the pathogenesis of pancreatitis

Raghuwansh P. Sah, Rajinder Dawra, Ashok Saluja

Research output: Contribution to journalReview article

101 Citations (Scopus)

Abstract

PURPOSE OF REVIEW: In this article, we review important advances in our understanding of the mechanisms of pancreatitis. RECENT FINDINGS: 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. SUMMARY: 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.

Original languageEnglish (US)
Pages (from-to)523-530
Number of pages8
JournalCurrent Opinion in Gastroenterology
Volume29
Issue number5
DOIs
StatePublished - Sep 1 2013
Externally publishedYes

Fingerprint

Pancreatitis
Trypsinogen
NF-kappa B
Trypsin
Acinar Cells
Chronic Pancreatitis
NFATC Transcription Factors
Ceruletide
Calcineurin
Genetic Models
Lung Injury
Interleukin-6
Cytokines
Calcium

Keywords

  • acute pancreatitis
  • chronic pancreatitis
  • nuclear factor kappa B
  • trypsin

ASJC Scopus subject areas

  • Gastroenterology

Cite this

New insights into the pathogenesis of pancreatitis. / Sah, Raghuwansh P.; Dawra, Rajinder; Saluja, Ashok.

In: Current Opinion in Gastroenterology, Vol. 29, No. 5, 01.09.2013, p. 523-530.

Research output: Contribution to journalReview article

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