Lab Invest. 2005 Jun 20; [Epub ahead of print] Related Articles, Links
Helicobacter felis-induced gastritis was suppressed in mice
overexpressing thioredoxin-1.
Kawasaki K, Nishio A, Nakamura H, Uchida K, [censored] T, Ohana M, Yoshizawa
H, Ohashi S, Tamaki H, Matsuura M, Asada M, Nishi T, Nakase H, Toyokuni
S, Liu W, Yodoi J, Okazaki K, Chiba T.
1Department of Gastroenterology and Endoscopic Medicine, Graduate
School of Medicine, Kyoto University, Kyoto, Japan.
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.Laboratory Investigation advance online publication,
20 June 2005; doi:10.1038/labinvest.3700305.
PMID: 15965489 [PubMed - as supplied by publisher]
--------------------------------------------------------------------------------
Who loves ya.
Tom