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 admi...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.展开更多
基金Supported by Federal funds from the National Cancer Institute(NCI)under Contract,No.HHSN261200800001E(to Chu FF)Research reported in this publication included work performed in the Animal Resources Center Core supported by the National Cancer Institute of the National Institutes of Health under award No.P30CA033572
文摘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.
