Helicobacter felis-induced gastritis was suppressed in mice overexpressing thioredoxin-1.
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.
Kawasaki
Kimio
K
Department of Gastroenterology and Endoscopic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Nishio
Akiyoshi
A
Nakamura
Hajime
H
Uchida
Kazushige
K
Fukui
Toshiro
T
Ohana
Masaya
M
Yoshizawa
Hazuki
H
Ohashi
Shinya
S
Tamaki
Hiroyuki
H
Matsuura
Minoru
M
Asada
Masanori
M
Nishi
Toshiki
T
Nakase
Hiroshi
H
Toyokuni
Shinya
S
Liu
Wenrui
W
Yodoi
Junji
J
Okazaki
Kazuichi
K
Chiba
Tsutomu
T
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*
D017931:DNA Primers; D013879:Thioredoxins; D006861:Hydrogen Peroxide