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Publication : NADPH oxidase-1 deficiency offers little protection in <i>Salmonella typhimurium</i>-induced typhlitis in mice.

First Author  Chu FF Year  2016
Journal  World J Gastroenterol Volume  22
Issue  46 Pages  10158-10165
PubMed ID  28028364 Mgi Jnum  J:271830
Mgi Id  MGI:6282670 Doi  10.3748/wjg.v22.i46.10158
Citation  Chu FF, et al. (2016) NADPH oxidase-1 deficiency offers little protection in Salmonella typhimurium-induced typhlitis in mice. World J Gastroenterol 22(46):10158-10165
abstractText  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 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 x 10(6) 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-alpha, 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.
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