Sensitization to and Challenge with Gliadin Induce Pancreatitis and Extrapancreatic Inflammation in HLA-DQ8 Mice: An Animal Model of Type 1 Autoimmune Pancreatitis.
- Author:
Sung Hoon MOON
1
;
Jihun KIM
;
Mi Young KIM
;
Do Hyun PARK
;
Tae Jun SONG
;
Sun A KIM
;
Sang Soo LEE
;
Dong Wan SEO
;
Sung Koo LEE
;
Myung Hwan KIM
Author Information
- Publication Type:Original Article
- Keywords: Autoimmune diseases; Pancreatitis; Celiac disease
- MeSH: Animals; Animals*; Atrophy; Autoimmune Diseases; Bile Ducts; Celiac Disease; Ceruletide; Eating; Edible Grain; Fibrosis; Gliadin*; Humans; Inflammation*; Kidney; Leukocytes; Lung; Mice*; Mice, Transgenic; Models, Animal*; Pancreatitis*; Plasma Cells; Salivary Glands
- From:Gut and Liver 2016;10(5):842-850
- CountryRepublic of Korea
- Language:English
- 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.
