Published online Dec 14, 2016. doi: 10.3748/wjg.v22.i46.10158
Peer-review started: July 25, 2016
First decision: September 20, 2016
Revised: October 9, 2016
Accepted: November 15, 2016
Article in press: November 16, 2016
Published online: December 14, 2016
To test whether Nox1 plays a role in typhlitis induced by Salmonella enterica serovar Typhimurium (S. Tm) in a mouse model.
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.
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.
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.
Core tip: Using Nox1-knockout mice (Nox1-KO), we examined the role of cecum Nox1 in Salmonella typhimurium (S. Tm) infection. Mice were rendered susceptible to infection with oral metronidazole. Four days after S. Tm inoculation, Nox1-KO mice had equal or slightly lower CFU/g cecum contents and equal or slightly less pathology by histological assessment than wild-type (WT) mice. Quantitative real-time PCR measure of mRNA levels for inflammatory cytokines Il-1β and TNF-α were significantly higher in S. Tm treated WT vs untreated mice but not in S. Tm treated Nox1-KO mice. Since Nox1 may have a role in inflammatory bowel disease, treating subjects with Nox1 inhibitors may not make patients vulnerable to pathogens.