title: The decrease in farnesoid X receptor, pregnane X receptor and constitutive androstane receptor in the liver after intestinal ischemia-reperfusion.
abstract: OBJECTIVE
  Intestinal ischemia-reperfusion (I/R) damages remote organs, including the liver, and promotes multi-organ failure (MOF). However, the molecular mechanisms underlying acute liver injury after intestinal I/R have not been completely elucidated. Farnesoid X receptor (FXR), pregnane X receptor (PXR) and constitutive androstane receptor (CAR) regulate metabolizing enzymes and transporters, and coordinately prevent hepatotoxicity reflecting an inability of appropriate excretion of endogenous toxic compounds. In this study, we assessed FXR, PXR and CAR expression levels and their localization levels in nuclei in the liver after intestinal I/R. We also investigated the effect of IL-6 on FXR, PXR and CAR expression levels and their localization levels in nuclei in in vitro experiments.
  
  
  METHODS
  We used intestinal I/R model rats. Moreover, HepG2 cells were used in in vitro study. Real-time PCR and Western blotting were used to assess mRNA and protein expression levels. Nuclear receptor localization in nuclei was analyzed by Western blotting using nuclear extracts.
  
  
  RESULTS
  FXR and PXR expression levels began to be decreased at 3 h, and FXR, PXR and CAR expression levels were decreased at 6 h after intestinal I/R. The localization levels of FXR, PXR and CAR in nuclei began to be decreased at 3 h, and all of them were decreased at 6 h after intestinal I/R. In HepG2 cells, FXR, PXR and CAR expression levels were decreased by 0.5-1 ng/mL, 0.5-100 ng/mL and 100 ng/mL IL-6 treatment for 24 h, respectively. FXR, PXR and CAR localization levels in nuclei were suppressed by 0.5-10 ng/mL, 10-100 ng/mL and 10-100 ng/mL IL-6 treatment for 24 h, respectively.
  
  
  CONCLUSIONS
  FXR, PXR and CAR expression levels are decreased in the liver after intestinal I/R. IL-6 is one of main causes the decreases in expressions of these receptors.
authors: Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan.
authors: Jiro
authors: J
authors: Ogura
authors: Yusuke
authors: Y
authors: Terada
authors: Takashi
authors: T
authors: Tsujimoto
authors: Takahiro
authors: T
authors: Koizumi
authors: Kaori
authors: K
authors: Kuwayama
authors: Hajime
authors: H
authors: Maruyama
authors: Asuka
authors: A
authors: Fujikawa
authors: Atsushi
authors: A
authors: Takaya
authors: Masaki
authors: M
authors: Kobayashi
authors: Shirou
authors: S
authors: Itagaki
authors: Natsuko
authors: N
authors: Takahashi
authors: Takeshi
authors: T
authors: Hirano
authors: Hiroaki
authors: H
authors: Yamaguchi
authors: Ken
authors: K
authors: Iseki
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D000090702:Constitutive Androstane Receptor; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D006801:Humans; D015850:Interleukin-6 / Q000008:administration & dosage / Q000378:metabolism; D007422:Intestines / Q000098:blood supply / Q000473:pathology; D008099:Liver / Q000473:pathology*; D008297:Male; D000077297:Pregnane X Receptor; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism*; D015427:Reperfusion Injury / Q000503:physiopathology*; D013997:Time Factors; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D000090702:Constitutive Androstane Receptor; D015850:Interleukin-6; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D000099150:Receptor, Farnesoid X-Activated