Cerulein-induced chronic pancreatitis does not require intra-acinar activation of trypsinogen in mice

Raghuwansh P Sah; Vikas Dudeja; Rajinder K Dawra; Ashok K Saluja

doi:10.1053/j.gastro.2013.01.041

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Cerulein-induced chronic pancreatitis does not require intra-acinar activation of trypsinogen in mice

Journal article

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Cerulein-induced chronic pancreatitis does not require intra-acinar activation of trypsinogen in mice

Raghuwansh P Sah, Vikas Dudeja, Rajinder K Dawra and Ashok K Saluja

Gastroenterology (New York, N.Y. 1943), Vol.144(5), pp.1076-1085.e2

05/01/2013

DOI: 10.1053/j.gastro.2013.01.041

PMID: 23354015

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Abstract

Premature activation of trypsinogen activation can cause pancreatic injury and has been associated with chronic pancreatitis (CP). Mice that lack intra-acinar activation of trypsinogen, such as trypsinogen-7-null (T(-/-)) and cathepsin B-null (CB(-/-)) mice, have been used to study trypsin-independent processes of CP development. We compared histologic features and inflammatory responses of pancreatic tissues from these mice with those from wild-type mice after the development of CP. CP was induced in wild-type, T(-/-), and CB(-/-) mice by twice-weekly induction of acute pancreatitis for 10 weeks; acute pancreatitis was induced by hourly intraperitoneal injections of cerulein (50 μg/kg × 6). Pancreatic samples were collected and evaluated by histologic and immunohistochemical analyses. Normal human pancreas samples, obtained from the islet transplant program at the University of Minnesota, were used as controls and CP samples were obtained from surgical resections. Compared with pancreatic tissues from wild-type mice, those from T(-/-) and CB(-/-) mice had similar levels of atrophy, histomorphologic features of CP, and chronic inflammation. All samples had comparable intra-acinar activation of nuclear factor (NF)-κB, a transcription factor that regulates the inflammatory response, immediately after injection of cerulein. Pancreatic tissue samples from patients with CP had increased activation of NF-κB (based on nuclear translocation of p65 in acinar cells) compared with controls. Induction of CP in mice by cerulein injection does not require intra-acinar activation of trypsinogen. Pancreatic acinar cells of patients with CP have increased levels of NF-κB activation compared with controls; regulation of the inflammatory response by this transcription factor might be involved in the pathogenesis of CP.

Acinar Cells - metabolism

Acinar Cells - pathology

Animals

Cells, Cultured

Ceruletide - toxicity

Immunohistochemistry

Mice

Mice, Inbred C57BL

Pancreas - metabolism

Pancreas - pathology

Pancreatitis, Chronic - chemically induced

Pancreatitis, Chronic - metabolism

Pancreatitis, Chronic - pathology

Trypsinogen - metabolism

Details

Title: Subtitle: Cerulein-induced chronic pancreatitis does not require intra-acinar activation of trypsinogen in mice
Creators: Raghuwansh P Sah - University of Minnesota
Vikas Dudeja - University of Minnesota
Rajinder K Dawra - University of Minnesota
Ashok K Saluja - University of Minnesota
Resource Type: Journal article
Publication Details: Gastroenterology (New York, N.Y. 1943), Vol.144(5), pp.1076-1085.e2
DOI: 10.1053/j.gastro.2013.01.041
PMID: 23354015
NLM abbreviation: Gastroenterology
ISSN: 0016-5085
eISSN: 1528-0012
Grant note: R01 DK092145 / NIDDK NIH HHS DK093047 / NIDDK NIH HHS DK092145 / NIDDK NIH HHS R01 CA124723 / NCI NIH HHS R01 DK093047 / NIDDK NIH HHS R01 DK058694 / NIDDK NIH HHS DK058694 / NIDDK NIH HHS
Language: English
Date published: 05/01/2013
Academic Unit: Anatomy and Cell Biology; Surgery
Record Identifier: 9985244679602771

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