title: BH3-only protein Bim is associated with the degree of Helicobacter pylori-induced gastritis and is localized to the mitochondria of inflammatory cells in the gastric mucosa.
abstract: BH3-only protein, Bim, is a pro-apoptotic protein that mediates mitochondria-dependent cell death. However, the role of Bim in Helicobacter pylori-associated gastritis remains unclear. This study aimed to assess the cellular localization of Bim and its possible role in H. pylori-induced gastritis. The study was conducted on biopsy specimens obtained from 80 patients who underwent upper gastrointestinal endoscopy (H. pylori-negative: n=30, positive: n=50). Association between Bim mRNA expression and severity of gastritis was evaluated and the localization of Bim was examined by immunofluorescence. Bim mRNA expression was positively correlated with the degree of gastritis, as defined by the Sydney system. Immunohistochemical analysis confirmed increased Bim expression in H. pylori-infected gastric mucosa compared with uninfected mucosa in both humans and mice. Bim localized in myeloperoxidase- and CD138-positive cells of H. pylori-infected lamina propria and submucosa of the gastric tract, indicating that this protein is predominantly expressed in neutrophils and plasma cells. In contrast, Bim did not localize in CD20-, CD3-, or CD68-positive cells. Bim was expressed in the mitochondria, where it was partially co-localized with activated Bax and cleaved-PARP. In conclusion, Bim is expressed in neutrophils and plasma cells in H. pylori-associated gastritis, where it may participate in the termination of inflammatory response by causing mitochondria-mediated apoptosis in specific leucocytes.
authors.affiliation: Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan; Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, 1-12-4 Sakamoto, Nagasaki City, Nagasaki, 852-8523, Japan. Electronic address: akazaway@nagasaki-u.ac.jp.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Akazawa
authors.affiliation: Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, 1-12-4 Sakamoto, Nagasaki City, Nagasaki, 852-8523, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Matsuda
authors.affiliation: Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Isomoto
authors.affiliation: Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Matsushima
authors.affiliation: Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kido
authors.affiliation: Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan.
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Urabe
authors.affiliation: Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Yamaghchi
authors.affiliation: Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Ohnita
authors.affiliation: Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan.
authors.forename: Fuminao
authors.initials: F
authors.lastname: Takeshima
authors.affiliation: Biostatistics Section, Division of Scientific Data Registry, Department of Radioisotope Medicine, Atomic Bomb Disease Institute, 1-12-4 Sakamoto, Nagasaki City, Nagasaki, 852-8523, Japan.
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Kondo
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinano-cho, Shinjyuku-ku, Tokyo, 1600000, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsugawa
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinano-cho, Shinjyuku-ku, Tokyo, 1600000, Japan.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Cardiovascular and Pulmonary Branch, NHLBI, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Joel
authors.initials: J
authors.lastname: Moss
authors.affiliation: Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakao
authors.affiliation: Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, 1-12-4 Sakamoto, Nagasaki City, Nagasaki, 852-8523, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakashima
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D005260:Female; D005753:Gastric Mucosa / Q000382:microbiology*; D005756:Gastritis / Q000382:microbiology*; D005786:Gene Expression Regulation; D016481:Helicobacter Infections / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D008928:Mitochondria / Q000382:microbiology; D009504:Neutrophils / Q000378:metabolism / Q000382:microbiology; D010950:Plasma Cells / Q000378:metabolism / Q000382:microbiology; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012329:RNA, Bacterial / Q000235:genetics / Q000302:isolation & purification*
chemical_list: D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D012329:RNA, Bacterial
keywords: Apoptosis; BH3-only protein; Bax; Bcl-2; Bim; Gastritis; Helicobacter pylori; Mitochondria