title: Helicobacter felis-induced gastritis was suppressed in mice overexpressing thioredoxin-1.
abstract: Thioredoxin-1 (TRX-1) is a redox-active protein involved in scavenging reactive oxygen species and regulating redox-sensitive transcription factors. TRX-1 is induced in various inflammatory conditions and shows cytoprotective action. We investigated the roles of TRX-1 in the host defense mechanism against Helicobacter felis (H. felis) infection. Transgenic (TG) mice overexpressing human TRX-1 and wild-type (WT) mice were orally inoculated with H. felis. After 2 months, histology, oxidative damage, and gene expression of several cytokines, including macrophage inflammatory protein-2 (MIP-2), a murine equivalent to interleukin (IL)-8, in the gastric mucosa were investigated. Furthermore, the effects of TRX-1 on oxidative stress and neutrophil migration were studied both in vivo and in vitro. The gastric mucosa was thickened in H. felis-infected WT mice, but not in infected TRX-1-TG mice. Histologically, all H. felis-infected WT mice developed moderate-to-severe gastritis, whereas the development of gastritis was significantly suppressed in infected TRX-1-TG mice. Oxidative damage markers, 8-hydroxy-2'-deoxyguanosine and malondialdehyde, increased in the stomach of infected WT mice, but not TRX-1-TG mice. Upregulation of IL-1beta and tumor necrosis factor-alpha gene expression in H. felis-infected TRX-1-TG mice was significantly lower than in WT mice. However, upregulation of MIP-2 and IL-7 was not different between the two groups. TRX-1 suppressed oxidative cytotoxicity and DNA damage, and inhibited neutrophil migration both in vivo and in vitro. The present study suggests that overexpression of TRX-1 suppresses H. felis-induced gastritis by inhibiting chemotaxis of neutrophils and reducing oxidative stress.
authors.affiliation: Department of Gastroenterology and Endoscopic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Kimio
authors.initials: K
authors.lastname: Kawasaki
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nishio
authors.forename: Hajime
authors.initials: H
authors.lastname: Nakamura
authors.forename: Kazushige
authors.initials: K
authors.lastname: Uchida
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fukui
authors.forename: Masaya
authors.initials: M
authors.lastname: Ohana
authors.forename: Hazuki
authors.initials: H
authors.lastname: Yoshizawa
authors.forename: Shinya
authors.initials: S
authors.lastname: Ohashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tamaki
authors.forename: Minoru
authors.initials: M
authors.lastname: Matsuura
authors.forename: Masanori
authors.initials: M
authors.lastname: Asada
authors.forename: Toshiki
authors.initials: T
authors.lastname: Nishi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakase
authors.forename: Shinya
authors.initials: S
authors.lastname: Toyokuni
authors.forename: Wenrui
authors.initials: W
authors.lastname: Liu
authors.forename: Junji
authors.initials: J
authors.lastname: Yodoi
authors.forename: Kazuichi
authors.initials: K
authors.lastname: Okazaki
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D005756:Gastritis / Q000382:microbiology*; D044922:Helicobacter felis / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018384:Oxidative Stress; D013879:Thioredoxins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D017931:DNA Primers; D013879:Thioredoxins; D006861:Hydrogen Peroxide