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Review
. 2012 Apr;41(3):353-7.
doi: 10.1097/MPA.0b013e3182321500.

Sterile inflammatory response in acute pancreatitis

Rafaz Hoque  1 , Ahsan F Malik, Fred Gorelick, Wajahat Z Mehal
Affiliations
Review

Sterile inflammatory response in acute pancreatitis

Rafaz Hoque et al. Pancreas. 2012 Apr.

Abstract

The initial injury in acute pancreatitis is characteristically sterile and results in acinar cells necrosis. Intracellular contents released from damaged cells into the extracellular space serve as damage-associated molecular patterns (DAMPs) that trigger inflammation. There is increasing evidence that this sterile inflammatory response mediated through DAMPs released from necrotic acinar cells is a key determinant of further pancreatic injury, remote organ injury, and disease resolution in experimental models. A number of DAMPS, including high-mobility group box protein 1, DNA, adenosine triphosphate and heat shock protein 70, have been shown to have a role in experimental pancreatitis. Many of these DAMPs are also detectable in the human pancreatitis. Genetic deletion and pharmacologic antagonism demonstrate that specific DAMP receptors, including Toll-like receptor (TLR) 4, TLR9, and P2X7, are also required for inflammation in experimental acute pancreatitis. Downstream DAMP-sensing components include nod-like receptor protein 3, caspase 1, interleukin-1β (IL-1), IL-18, and IL-1 receptor, and also are required for full experimental pancreatitis. These DAMP-mediated pathways provide novel therapeutic targets using antagonists of TLRs and other receptors.

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Figures

Figure 1
Figure 1
The sterile inflammatory response in acute pancreatitis. In acute pancreatitis, injured parenchymal cells release DAMPs. These are Signal 1 and Signal 2 for respective receptors in DAMP sensing cells which then produce IL-1β and IL-18. The latter effector cytokines stimulate pro-inflammatory responses in other immune cells promoting further cell death in the pancreas and immune injury in distant organs.
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References

    1. Bonilla FA, Oettgen HC. Adaptive immunity. J Allergy Clin Immunol. 2010;125:S33–40. - PubMed
    1. Chen GY, Nunez G. Sterile inflammation: sensing and reacting to damage. Nat Rev Immunol. 2010;10:826–837. - PMC - PubMed
    1. Iyer SS, Pulskens WP, Sadler JJ, et al. Necrotic cells trigger a sterile inflammatory response through the Nlrp3 inflammasome. Proc Natl Acad Sci U S A. 2009;106:20388–20393. - PMC - PubMed
    1. Piccinini AM, Midwood KS. DAMPening inflammation by modulating TLR signalling. Mediators Inflamm. 2010:672395. - PMC - PubMed
    1. Zhang Q, Raoof M, Chen Y, et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010;464:104–107. - PMC - PubMed

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