| First Author | Dawra R | Year | 2011 |
| Journal | Gastroenterology | Volume | 141 |
| Issue | 6 | Pages | 2210-2217.e2 |
| PubMed ID | 21875495 | Mgi Jnum | J:330333 |
| Mgi Id | MGI:7367636 | Doi | 10.1053/j.gastro.2011.08.033 |
| Citation | Dawra R, et al. (2011) Intra-acinar trypsinogen activation mediates early stages of pancreatic injury but not inflammation in mice with acute pancreatitis. Gastroenterology 141(6):2210-2217.e2 |
| abstractText | BACKGROUND & AIMS: The role of trypsinogen activation in the pathogenesis of acute pancreatitis (AP) has not been clearly established. METHODS: We generated and characterized mice lacking trypsinogen isoform 7 (T7) gene (T(-/-)). The effects of pathologic activation of trypsinogen were studied in these mice during induction of AP with cerulein. Acinar cell death, tissue damage, early intra-acinar activation of the transcription factor nuclear factor kappaB (NF-kappaB), and local and systemic inflammation were compared between T(-/-) and wild-type mice with AP. RESULTS: Deletion of T7 reduced the total trypsinogen content by 60% but did not affect physiologic function. T(-/-) mice lacked pathologic activation of trypsinogen, which occurs within acinar cells during early stages of AP progression. Absence of trypsinogen activation in T(-/-) mice led to near complete inhibition of acinar cell death in vitro and a 50% reduction in acinar necrosis during AP progression. However, T(-/-) mice had similar degrees of local and systemic inflammation during AP progression and comparable levels of intra-acinar NF-kappaB activation, which was previously shown to occur concurrently with trypsinogen activation during early stages of pancreatitis. CONCLUSIONS: T7 is activated during pathogenesis of AP in mice. Intra-acinar trypsinogen activation leads to acinar death during early stages of pancreatitis, which accounts for 50% of the pancreatic damage in AP. However, progression of local and systemic inflammation in AP does not require trypsinogen activation. NF-kappaB is activated early in acinar cells, independently of trypsinogen activation, and might be responsible for progression of AP. |
