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Regulation of liver CYPs in the course of Citrobacter rodentium‐induced inflammation/infection in C57BL/6 mouse colon
Author(s) -
Chaluvadi Madhusudana Rao,
Richardson Terrilyn A,
Sherman Melanie A,
Antonovic Leposava,
Strobel Henry W,
Kalman Daniel,
Morgan Edward T
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1180-c
We found earlier the murine intestinal pathogen Citrobacter rodentium in C3H/HeOuJ mice causes a unique pattern of hepatic cytochrome P450 (CYP) regulation that is Toll‐like receptor 4 independent. The aim of this study was to investigate the regulation of hepatic cytochrome P450 (CYP) mRNAs, proteins, and blood cytokines, during the time course of infection induced by oral administration of C. rodentium to C57BL/6 mice, which are more resistant to C. rodentium pathology and morbidity. Female C57BL/6 mice were infected with C. rodentium in their drinking water for 16 hr. Groups of mice were sacrificed at 7, 10, 15 and 24 days post infection, and the livers analyzed for mRNA and protein levels of CYPs. Many of the CYPs analyzed were down regulated at both mRNA and protein levels at 7 and 10 days post infection while CYP4F18 was induced. The pattern of CYP regulation was almost identical to that seen previously in the HeOuJ mice. Serum levels of IL‐2, IL‐6, IFNγ, TNFα, MIP1α and MCP1 were significantly elevated in the plasma at 7 and 10 days post infection. CYP mRNAs, proteins and cytokines returned to normal levels as the infection resolved. These data confirm that the pattern of CYP regulation is maintained in mice that have moderate symptoms of infection, and are consistent with the idea that the regulation is mediated by serum inflammatory cytokines and/or chemokines. Supported by NIH grants DK072372 (ETM) and NS44174 (HWS).