NADPH oxidase-1 deficiency offers little protection in Salmonella typhimurium-induced typhlitis in mice

• Published in: World journal of gastroenterology : WJG 2016-12, Vol.22 (46), p.10158-10165
• Main Authors: Chu, Fong-Fong, Esworthy, R Steven, Doroshow, James H, Shen, Binghui
• Format: Article
• Language: English
• Subjects: Alkaline Phosphatase - genetics; Animals; Basic Study; Cecum - metabolism; Cecum - pathology; Disease Models, Animal; Dual Oxidases; Gene Expression; Genetic Predisposition to Disease; Interleukin-1beta - genetics; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; NADH, NADPH Oxidoreductases - genetics; NADPH Oxidase 1; NADPH Oxidases - genetics; Real-Time Polymerase Chain Reaction; RNA, Messenger - metabolism; Salmonella Infections - genetics; Salmonella Infections - metabolism; Salmonella Infections - pathology; Salmonella typhimurium; Tumor Necrosis Factor-alpha - genetics; Typhlitis - genetics; Typhlitis - metabolism; Typhlitis - pathology
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v22.i46.10158

AIM To test whether Nox1 plays a role in typhlitis induced by Salmonella enterica serovar Typhimurium(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 m RNA/c DNA 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 × 106 CFU) 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. CONCLUSION 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.