Pancreatic secretory trypsin inhibitor I reduces the severity of chronic pancreatitis in mice overexpressing interleukin-1β in the pancreas.

Published

Journal Article

IL-1β is believed to play a pathogenic role in the development of pancreatitis. Expression of human IL-1β in pancreatic acinar cells produces chronic pancreatitis, characterized by extensive intrapancreatic inflammation, atrophy, and fibrosis. To determine if activation of trypsinogen is important in the pathogenesis of chronic pancreatitis in this model, we crossed IL-1β transgenic [Tg(IL1β)] mice with mice expressing a trypsin inhibitor that is normally produced in rat pancreatic acinar cells [pancreatic secretory trypsin inhibitor (PTSI) I]. We previously demonstrated that transgenic expression of PSTI-I [Tg(Psti1)] increased pancreatic trypsin inhibitor activity by 190%. Tg(IL1β) mice were found to have marked pancreatic inflammation, characterized by histological changes, including acinar cell loss, inflammatory cell infiltration, and fibrosis, as well as elevated myeloperoxidase activity and elevated pancreatic trypsin activity, as early as 6 wk of age. In contrast to Tg(IL1β) mice, pancreatitis was significantly less severe in dual-transgenic [Tg(IL1β)-Tg(Psti1)] mice expressing IL-1β and PSTI-I in pancreatic acinar cells. These findings indicate that overexpression of PSTI-I reduces the severity of pancreatitis and that pancreatic trypsin activity contributes to the pathogenesis of an inflammatory model of chronic pancreatitis.

Full Text

Duke Authors

Cited Authors

  • Romac, JM-J; Shahid, RA; Choi, SS; Karaca, GF; Westphalen, CB; Wang, TC; Liddle, RA

Published Date

  • March 2012

Published In

Volume / Issue

  • 302 / 5

Start / End Page

  • G535 - G541

PubMed ID

  • 22173919

Pubmed Central ID

  • 22173919

Electronic International Standard Serial Number (EISSN)

  • 1522-1547

International Standard Serial Number (ISSN)

  • 0193-1857

Digital Object Identifier (DOI)

  • 10.1152/ajpgi.00287.2011

Language

  • eng