| Budget Amount *help |
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2015: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
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| Outline of Final Research Achievements |
Although bacterial translocation is sometimes seen in patients with severe pancreatitis, it remains largely unknown how innate immune responses against intestinal microflora regulate the development of pancreatitis. In our previous study, we identified nucleotide-binding oligomerization domain 1 (NOD1) as a pathogenic innate immune receptor for experimental pancreatitis. In this study, we developed a new model of chronic pancreatitis induced by repeated administration of NOD1 ligand and cerulein, a cholecystokinin receptor (CCKR) agonist. The development of chronic pancreatitis induced by synergistic activation of CCKR and NOD1 requires IL-33 and IFN-beta production by acinar cells. IL-33 produced by acinar cells induces pro-fibrogenic factors such as IL-13 by Th2 cells whereas IFN-beta induces Th1 responses. Therefore, synergistic activation of NOD1 and CCKR results in IL-33-dependent pancreatitis characterized by Th1 and Th2 responses.
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