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All pregnant mice except controls were i.p. injected with LPS (100 \u03bcg\/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-\u03b1 in maternal serum and amniotic fluid. Moreover, OCA significantly attenuated LPS-induced upregulation of placental proinflammatory genes including Tnf-\u03b1, Il-1\u03b2, 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-\u03baB 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.<\/jats:p>","DOI":"10.4049\/jimmunol.1601331","type":"journal-article","created":{"date-parts":[[2016,11,8]],"date-time":"2016-11-08T03:14:29Z","timestamp":1478574869000},"page":"4762-4770","source":"Crossref","is-referenced-by-count":34,"title":["Obeticholic Acid Protects against Lipopolysaccharide-Induced Fetal Death and Intrauterine Growth Restriction through Its Anti-Inflammatory Activity"],"prefix":"10.1093","volume":"197","author":[{"given":"Yuan-Hua","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Toxicology, Anhui Medical University , Hefei 230032,","place":["China"]},{"name":"Laboratory of Environmental Toxicology , Hefei 230032,","place":["China"]},{"name":"Department of Histology and Embryology, Anhui Medical University , Hefei 230032,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Guang","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Anhui Medical University , Hefei 230032,","place":["China"]},{"name":"Laboratory of Environmental Toxicology , Hefei 230032,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Anhui Medical University , Hefei 230032,","place":["China"]},{"name":"Laboratory of Environmental Toxicology , Hefei 230032,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Anhui Medical University , Hefei 230032,","place":["China"]},{"name":"Laboratory of Environmental Toxicology , Hefei 230032,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Anhui Medical University , Hefei 230032,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gui-Bin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Anhui Medical University , Hefei 230032,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing-Li","family":"Bo","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Anhui Medical University , Hefei 230032,","place":["China"]},{"name":"Laboratory of Environmental Toxicology , Hefei 230032,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Anhui Medical University , Hefei 230032,","place":["China"]},{"name":"Laboratory of Environmental Toxicology , Hefei 230032,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Anhui Medical University , Hefei 230032,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"De-Xiang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Anhui Medical University , Hefei 230032,","place":["China"]},{"name":"Laboratory of Environmental Toxicology , Hefei 230032,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2016,12,15]]},"reference":[{"key":"2025030618361139200_r1","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1210\/er.2014-1100","article-title":"TLR4 at the crossroads of nutrients, gut microbiota, and metabolic inflammation","volume":"36","author":"Velloso","year":"2015","journal-title":"Endocr. 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