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Molecular Medicine

, Volume 20, Issue 1, pp 466–477 | Cite as

Cell Death and DAMPs in Acute Pancreatitis

  • Rui Kang
  • Michael T. Lotze
  • Herbert J. Zeh
  • Timothy R. Billiar
  • Daolin Tang
Review Article

Abstract

Cell death and inflammation are key pathologic responses of acute pancreatitis (AP), the leading cause of hospital admissions for gastrointestinal disorders. It is becoming increasingly clear that damage-associated molecular pattern molecules (DAMPs) play an important role in the pathogenesis of AP by linking local tissue damage to systemic inflammation syndrome. Endogenous DAMPs released from dead, dying or injured cells initiate and extend sterile inflammation via specific pattern recognition receptors. Inhibition of the release and activity of DAMPs (for example, high mobility group box 1, DNA, histones and adenosine triphosphate) provides significant protection against experimental AP. Moreover, increased serum levels of DAMPs in patients with AP correlate with disease severity. These findings provide novel insight into the mechanism, diagnosis and management of AP. DAMPs might be an attractive therapeutic target in AP.

Notes

Acknowledgments

We apologize to the researchers who were not referenced due to space limitations. We thank Christine Heiner (Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA) for her critical reading of the manuscript. This work was supported by the National Institutes of Health (R01CA160417 to D Tang; R01CA181450 to HJ Zeh/MT Lotze) and a 2013 Pancreatic Cancer Action Network-AACR Career Development Award (grant number 13-20-25-TANG). The work supporting the findings reviewed in this manuscript was aided by core support from the University of Pittsburgh Cancer Institute (NIH grant P30CA047904).

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Authors and Affiliations

  1. 1.Department of SurgeryUniversity of PittsburghPittsburghUSA

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