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Sensing of commensal organisms by the intracellular sensor NOD1 mediates experimental pancreatitis.


ABSTRACT: The intracellular sensor NOD1 has important host-defense functions relating to a variety of pathogens. Here, we showed that this molecule also participates in the induction of a noninfectious pancreatitis via its response to commensal organisms. Pancreatitis induced by high-dose cerulein (a cholecystokinin receptor agonist) administration depends on NOD1 stimulation by gut microflora. To analyze this NOD1 activity, we induced pancreatitis by simultaneous administration of a low dose of cerulein (that does not itself induce pancreatitis) and FK156, an activator of NOD1 that mimics the effect of gut bacteria that have breached the mucosal barrier. The pancreatitis was dependent on acinar cell production of the chemokine MCP-1 and the intrapancreatic influx of CCR2(+) inflammatory cells. Moreover, MCP-1 production involved activation of the transcription factors NF-?B and STAT3, each requiring complementary NOD1 and cerulein signaling. These studies indicate that gut commensals enable noninfectious pancreatic inflammation via NOD1 signaling in pancreatic acinar cells.

SUBMITTER: Tsuji Y 

PROVIDER: S-EPMC3523885 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Sensing of commensal organisms by the intracellular sensor NOD1 mediates experimental pancreatitis.

Tsuji Yoshihisa Y   Watanabe Tomohiro T   Kudo Masatoshi M   Arai Hidenori H   Strober Warren W   Chiba Tsutomu T  

Immunity 20120816 2


The intracellular sensor NOD1 has important host-defense functions relating to a variety of pathogens. Here, we showed that this molecule also participates in the induction of a noninfectious pancreatitis via its response to commensal organisms. Pancreatitis induced by high-dose cerulein (a cholecystokinin receptor agonist) administration depends on NOD1 stimulation by gut microflora. To analyze this NOD1 activity, we induced pancreatitis by simultaneous administration of a low dose of cerulein  ...[more]

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