title: NADPH oxidase-1 deficiency offers little protection inSalmonella typhimurium-induced typhlitis in mice.
abstract: OBJECTIVE
  To test whether Nox1 plays a role in typhlitis induced bySalmonella enterica serovarTyphimurium (S. Tm) in a mouse model.
  
  
  METHODS
  Eight-week-old male wild-type (WT) and Nox1 knockout (KO) C57BL6/J (B6) mice were administered metronidazole water for 4 d to make them susceptible to S. Tm infection by the oral route. The mice were given plain water and administered with 4 different doses of S. Tm by oral gavage. The mice were followed for another 4 d. From the time of the metronidazole application, the mice were observed twice daily and weighed daily. The ileum, cecum and colon were removed for sampling at the fourth day post-inoculation. Portions of all three tissues were fixed for histology and placed in RNAlater for mRNA/cDNA preparation and quantitative real-time PCR. The contents of the cecum were recovered for estimation of S. Tm CFU.
  
  
  RESULTS
  We found Nox1-knockout (Nox1-KO) mice were not more sensitive to S. Tm colonization and infection than WT B6 mice. This conclusion is based on the following observations: (1) S. Tm-infection induced similar weight loss in Nox1-KO mice compared to WT mice; (2) the same S. Tm CFU was recovered from the cecal content of Nox1-KO and WT mice regardless of the inoculation dose, except the lowest inoculation dose (2 × 106CFU) for which the Nox1-KO had one-log lower CFU than WT mice; (3) there is no difference in cecal pathology between WT and Nox1-KO groups; and (4) there are no S. Tm infection-induced changes in gene expression levels (IL-1b, TNF-α, and Duox2) between WT and Nox1-KO groups. The Alpi gene expression was more suppressed by S. Tm treatment in WT than the Nox1-KO cecum.
  
  
  CONCLUSIONS
  Nox1 does not protect mice from S. Tm colonization. Nox1-KO provides a very minor protective effect against S. Tm infection. Using NOX1-specific inhibitors for colitis therapy should not increase risks in bacterial infection.
authors.affiliation: Fong-Fong Chu, Department of Gastroenterology and Hepatology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, Henan Province, China.
authors.forename: Fong-Fong
authors.initials: FF
authors.lastname: Chu
authors.affiliation: Fong-Fong Chu, Department of Gastroenterology and Hepatology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, Henan Province, China.
authors.forename: R Steven
authors.initials: RS
authors.lastname: Esworthy
authors.affiliation: Fong-Fong Chu, Department of Gastroenterology and Hepatology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, Henan Province, China.
authors.forename: James H
authors.initials: JH
authors.lastname: Doroshow
authors.affiliation: Fong-Fong Chu, Department of Gastroenterology and Hepatology, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, Henan Province, China.
authors.forename: Binghui
authors.initials: B
authors.lastname: Shen
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics; D000818:Animals; D002432:Cecum / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D000074623:Dual Oxidases; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D053583:Interleukin-1beta / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics*; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012480:Salmonella Infections / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012486:Salmonella typhimurium; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D053706:Typhlitis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000074623:Dual Oxidases; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases; C000614711:NOX1 protein, mouse; C519130:Duox1 protein, mouse; D000469:Alkaline Phosphatase
keywords: Goblet cells; Knockout mouse; NADPH Oxidase-1; Reactive oxygen species; Salmonella typhimurium