BACKGROUND AND AIMS: Major histocompatibility complex class II deficient (Aalpha0/0) mice have decreased CD4+ T cells, making them immunologically similar to patients with acquired immunodeficiency syndrome (AIDS). Both patients with AIDS and Aalpha0/0 mice have hypertrophic gastric folds. To clarify the mechanism of gastric mucosal hyperplasia, we investigated the pathophysiology and the role of the innate immunity in the stomach of Aalpha0/0 mice. METHODS: Stomachs from 1-6 month old Aalpha0/0 mice, kept under specific pathogen free conditions, were examined at 1 month intervals histologically and immunohistochemically. Gene expression of proinflammatory cytokines, Toll-like receptors (TLRs), cyclooxygenase (COX)-2, and myeloperoxidase (MPO) activity in the gastric mucosa was investigated. Serum gastrin levels and gastric acidity were measured. Bacterial culture of the stomach was performed. To clarify the roles of hypergastrinaemia in the gastric mucosa, a gastrin receptor antagonist (AG041R) was administered. RESULTS: Aalpha0/0 mice had a diffusely thick corpus mucosa with infiltration of CD11b+ granulocytes and macrophages. Anti-Ki67 staining demonstrated expansion of the proliferating neck zone. Gene expression of interleukin 1beta, interferon gamma, TLR-2, TLR-4, and COX-2 were upregulated, and MPO activity was increased. Only a small amount of non-pathogenic bacteria was detected in the stomach. Serum gastrin levels and Reg-Ialpha positive cells in the gastric mucosa increased, despite normal gastric acidity. After treatment with AG041R, gastric mucosal thickness was significantly reduced. CONCLUSION: Persistent activation of innate immunity in the stomach induced gastric mucosal hyperplasia through upregulation of gastrin synthesis in Aalpha0/0 mice, suggesting a pathophysiology similar to the gastric changes in patients with AIDS.
BACKGROUND AND AIMS: Major histocompatibility complex class II deficient (Aalpha0/0) mice have decreased CD4+ T cells, making them immunologically similar to patients with acquired immunodeficiency syndrome (AIDS). Both patients with AIDS and Aalpha0/0 mice have hypertrophic gastric folds. To clarify the mechanism of gastric mucosal hyperplasia, we investigated the pathophysiology and the role of the innate immunity in the stomach of Aalpha0/0 mice. METHODS: Stomachs from 1-6 month old Aalpha0/0 mice, kept under specific pathogen free conditions, were examined at 1 month intervals histologically and immunohistochemically. Gene expression of proinflammatory cytokines, Toll-like receptors (TLRs), cyclooxygenase (COX)-2, and myeloperoxidase (MPO) activity in the gastric mucosa was investigated. Serum gastrin levels and gastric acidity were measured. Bacterial culture of the stomach was performed. To clarify the roles of hypergastrinaemia in the gastric mucosa, a gastrin receptor antagonist (AG041R) was administered. RESULTS: Aalpha0/0 mice had a diffusely thick corpus mucosa with infiltration of CD11b+ granulocytes and macrophages. Anti-Ki67 staining demonstrated expansion of the proliferating neck zone. Gene expression of interleukin 1beta, interferon gamma, TLR-2, TLR-4, and COX-2 were upregulated, and MPO activity was increased. Only a small amount of non-pathogenic bacteria was detected in the stomach. Serum gastrin levels and Reg-Ialpha positive cells in the gastric mucosa increased, despite normal gastric acidity. After treatment with AG041R, gastric mucosal thickness was significantly reduced. CONCLUSION: Persistent activation of innate immunity in the stomach induced gastric mucosal hyperplasia through upregulation of gastrin synthesis in Aalpha0/0 mice, suggesting a pathophysiology similar to the gastric changes in patients with AIDS.
Authors: M Asahara; S Mushiake; S Shimada; H Fukui; Y Kinoshita; C Kawanami; T Watanabe; S Tanaka; A Ichikawa; Y Uchiyama; Y Narushima; S Takasawa; H Okamoto; M Tohyama; T Chiba Journal: Gastroenterology Date: 1996-07 Impact factor: 22.682
Authors: Marcin Magierowski; Katarzyna Magierowska; Magdalena Hubalewska-Mazgaj; Zbigniew Sliwowski; Grzegorz Ginter; Robert Pajdo; Anna Chmura; Slawomir Kwiecien; Tomasz Brzozowski Journal: Br J Pharmacol Date: 2017-08-30 Impact factor: 8.739
Authors: Vesa-Matti Pohjanen; Olli-Pekka Koivurova; Heikki Huhta; Olli Helminen; Johanna M Mäkinen; Jari M Karhukorpi; Tapio Joensuu; Pentti O Koistinen; Jarno M Valtonen; Seppo E Niemelä; Riitta A Karttunen; Tuomo J Karttunen Journal: PLoS One Date: 2015-07-10 Impact factor: 3.240
Authors: Hilda Wong; Thomas Yau; Pierre Chan; Irene O L Ng; Gavin Chan; Peter Hui; W L Law; C M Lo; Antony J Hedley; Richard J Epstein Journal: Pathol Oncol Res Date: 2009-08-20 Impact factor: 3.201