Sensitization to and challenge with gliadin induce pancreatitis and extrapancreatic inflammation in HLA-DQ8 mice: An animal model of type 1 autoimmune pancreatitis

Authors

Sung Hoon Moon, Hallym University Sacred Heart Hospital
Jihun Kim, University of Ulsan, College of Medicine
Mi Young Kim, College of Medicine, Pochon CHA University
Do Hyun Park, University of Ulsan, College of Medicine
Tae Jun Song, University of Ulsan, College of Medicine
Sun A. Kim, University of Ulsan, College of Medicine
Sang Soo Lee, University of Ulsan, College of Medicine
Dong Wan Seo, University of Ulsan, College of Medicine
Sung Koo Lee, University of Ulsan, College of Medicine
Myung Hwan Kim, University of Ulsan, College of Medicine

Document Type

Journal Article

Publication Date

9-1-2016

Journal

Gut and Liver

Volume

10

Issue

5

DOI

10.5009/gnl15484

Keywords

Autoimmune diseases; Celiac disease; Pancreatitis

Abstract

Background/Aims: The aim of this study was to establish a pathogenetic mechanism of pancreatitis in celiac disease and IgG4-related disease using gluten-sensitive human leukocyte antigen (HLA)-DQ8 transgenic mice. Methods: Transgenic mice expressing HLA-DQ8 genes were utilized. Control mice were not sensitized but were fed gliadin-free rice cereal. Experimental groups consisted of gliadin-sensitized and gliadin-challenged mice; nonsensitized mice with cerulein hyperstimulation; and gliadin-sensitized and gliadinchallenged mice with cerulein hyperstimulation. Results: Gliadin-sensitized and gliadin-challenged mice with cerulein hyperstimulation showed significant inflammatory cell infiltrates, fibrosis and acinar atrophy compared with the control mice and the other experimental groups. The immunohistochemical analysis showed greater IgG1-positive plasma cells in the inflammatory infiltrates of gliadin-sensitized and gliadin-challenged mice with cerulein hyperstimulation compared with the control mice and the other experimental groups. Gliadin-sensitized and gliadin-challenged mice with cerulein hyperstimulation or gliadin-sensitized and gliadinchallenged mice showed IgG1-stained inflammatory cell infiltrates in the extrapancreatic organs, including the bile ducts, salivary glands, kidneys, and lungs. Conclusions: Gliadinsensitization and cerulein hyperstimulation of gluten-sensitive HLA-DQ8 transgenic mice resulted in pancreatitis and extrapancreatic inflammation. This animal model suggests that chronic gliadin ingestion in a susceptible individual with the HLA-DQ8 molecule may be associated with pancreatitis and extrapancreatic inflammation.

APA Citation

Moon, S., Kim, J., Kim, M., Park, D., Song, T., Kim, S., Lee, S., Seo, D., Lee, S., & Kim, M. (2016). Sensitization to and challenge with gliadin induce pancreatitis and extrapancreatic inflammation in HLA-DQ8 mice: An animal model of type 1 autoimmune pancreatitis. Gut and Liver, 10 (5). http://dx.doi.org/10.5009/gnl15484