PMID- 27821667
OWN - NLM
STAT- MEDLINE
DCOM- 20170811
LR  - 20181202
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 197
IP  - 12
DP  - 2016 Dec 15
TI  - Obeticholic Acid Protects against Lipopolysaccharide-Induced Fetal Death and 
      Intrauterine Growth Restriction through Its Anti-Inflammatory Activity.
PG  - 4762-4770
AB  - Farnesoid X receptor (FXR) is expressed in human and rodent placentas. 
      Nevertheless, its function remains obscure. This study investigated the effects 
      of obeticholic acid (OCA), a novel synthetic FXR agonist, on LPS-induced fetal 
      death and intrauterine growth restriction. All pregnant mice except controls were 
      i.p. injected with LPS (100 mug/kg) daily from gestational day (GD) 15 to GD17. 
      Some pregnant mice were orally administered with OCA (5 mg/kg) daily from GD13 to 
      GD17. As expected, placental FXR signaling was activated by OCA. OCA pretreatment 
      protected against LPS-induced fetal death. In addition, OCA pretreatment 
      alleviated LPS-induced reduction of fetal weight and crown-rump length. 
      Additional experiments showed that OCA inhibited LPS-evoked TNF-alpha in maternal 
      serum and amniotic fluid. Moreover, OCA significantly attenuated LPS-induced 
      upregulation of placental proinflammatory genes including Tnf-alpha, Il-1beta, IL-6, 
      Il-12, Mip-2, Kc, and Mcp-1 By contrast, OCA elevated anti-inflammatory cytokine 
      IL-10 in maternal serum, amniotic fluid, and placenta. Further analysis showed 
      that OCA blocked nuclear translocation of NF-kappaB p65 and p50 subunits in 
      trophoblast giant cells of the labyrinth zone. These results provide a 
      mechanistic explanation for placental FXR-mediated anti-inflammatory activity. 
      Overall, this study provides evidence for roles of FXR as an important regulator 
      of placental inflammation.
CI  - Copyright (c) 2016 by The American Association of Immunologists, Inc.
FAU - Chen, Yuan-Hua
AU  - Chen YH
AD  - Department of Toxicology, Anhui Medical University, Hefei 230032, China.
AD  - Laboratory of Environmental Toxicology, Hefei 230032, China; and.
AD  - Department of Histology and Embryology, Anhui Medical University, Hefei 230032, 
      China.
FAU - Hu, Xiao-Guang
AU  - Hu XG
AD  - Department of Toxicology, Anhui Medical University, Hefei 230032, China.
AD  - Laboratory of Environmental Toxicology, Hefei 230032, China; and.
FAU - Zhou, Yan
AU  - Zhou Y
AD  - Department of Toxicology, Anhui Medical University, Hefei 230032, China.
AD  - Laboratory of Environmental Toxicology, Hefei 230032, China; and.
FAU - Yu, Zhen
AU  - Yu Z
AD  - Department of Toxicology, Anhui Medical University, Hefei 230032, China.
AD  - Laboratory of Environmental Toxicology, Hefei 230032, China; and.
FAU - Fu, Lin
AU  - Fu L
AD  - Department of Toxicology, Anhui Medical University, Hefei 230032, China.
FAU - Zhang, Gui-Bin
AU  - Zhang GB
AD  - Department of Toxicology, Anhui Medical University, Hefei 230032, China.
FAU - Bo, Qing-Li
AU  - Bo QL
AD  - Department of Toxicology, Anhui Medical University, Hefei 230032, China.
AD  - Laboratory of Environmental Toxicology, Hefei 230032, China; and.
FAU - Wang, Hua
AU  - Wang H
AD  - Department of Toxicology, Anhui Medical University, Hefei 230032, China.
AD  - Laboratory of Environmental Toxicology, Hefei 230032, China; and.
FAU - Zhang, Cheng
AU  - Zhang C
AD  - Department of Toxicology, Anhui Medical University, Hefei 230032, China.
FAU - Xu, De-Xiang
AU  - Xu DX
AD  - Department of Toxicology, Anhui Medical University, Hefei 230032, China; 
      xudex@126.com.
AD  - Laboratory of Environmental Toxicology, Hefei 230032, China; and.
LA  - eng
PT  - Journal Article
DEP - 20161107
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0462Z4S4OZ (obeticholic acid)
RN  - 0C5V0MRU6P (farnesoid X-activated receptor)
RN  - 0GEI24LG0J (Chenodeoxycholic Acid)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*administration & dosage/pharmacology
MH  - Chenodeoxycholic Acid/administration & dosage/*analogs & derivatives/pharmacology
MH  - Cytokines/metabolism
MH  - Endotoxemia/*complications/immunology
MH  - Female
MH  - Fetal Death/etiology/*prevention & control
MH  - Fetal Growth Retardation/etiology/*prevention & control
MH  - Humans
MH  - Inflammation Mediators/metabolism
MH  - Lipopolysaccharides/immunology
MH  - Male
MH  - Mice, Inbred ICR
MH  - NF-kappa B/metabolism
MH  - Placenta/*drug effects/immunology
MH  - Pregnancy
MH  - Receptors, Cytoplasmic and Nuclear/agonists/*metabolism
MH  - Signal Transduction
EDAT- 2016/11/09 06:00
MHDA- 2017/08/12 06:00
CRDT- 2016/11/09 06:00
PHST- 2016/08/02 00:00 [received]
PHST- 2016/10/08 00:00 [accepted]
PHST- 2016/11/09 06:00 [pubmed]
PHST- 2017/08/12 06:00 [medline]
PHST- 2016/11/09 06:00 [entrez]
AID - jimmunol.1601331 [pii]
AID - 10.4049/jimmunol.1601331 [doi]
PST - ppublish
SO  - J Immunol. 2016 Dec 15;197(12):4762-4770. doi: 10.4049/jimmunol.1601331. Epub 
      2016 Nov 7.