Gut Liver.
2016 Sep;10(5):842-850. 10.5009/gnl15484.
Sensitization to and Challenge with Gliadin Induce Pancreatitis and Extrapancreatic Inflammation in HLA-DQ8 Mice: An Animal Model of Type 1 Autoimmune Pancreatitis
- Affiliations
-
- 1Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Korea.
- 2Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
- 3Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea.
- 4Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. mhkim@amc.seoul.kr
- KMID: 2412084
- DOI: http://doi.org/10.5009/gnl15484
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 gliadin-challenged 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 gliadin-challenged mice showed IgG1-stained inflammatory cell infiltrates in the extrapancreatic organs, including the bile ducts, salivary glands, kidneys, and lungs.
CONCLUSIONS
Gliadin-sensitization 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.
Keyword
MeSH Terms
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Animals
Autoimmune Diseases/*immunology
Ceruletide/immunology
Disease Models, Animal
Gliadin/*immunology
HLA-DQ Antigens/*immunology
*Hypersensitivity
Immunoglobulin G/blood
Inflammation/immunology
Mice
Mice, Transgenic
Pancreatitis/chemically induced/*immunology
HLA-DQ Antigens
Immunoglobulin G
Ceruletide
Gliadin
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