{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:28:15Z","timestamp":1787030895419,"version":"build-2736575974"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2019,9,1]],"date-time":"2019-09-01T00:00:00Z","timestamp":1567296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>It is increasingly recognized that excessive glucocorticoids induce fetal intrauterine growth restriction (IUGR). Placental 11\u03b2-hydroxysteroid dehydrogenase 2 (11\u03b2-HSD2), a glucocorticoid-catalyzing enzyme, prevents active glucocorticoids from maternal circulation into the fetus, thus protecting against IUGR. Previous studies demonstrated gestational LPS exposure caused fetal IUGR. The aim of the current study was to investigate the effects of LPS on 11\u03b2-HSD2 in mice placentas and human placental trophoblasts. Pregnant ICR(CD-1) mice were i.p. injected with LPS (200 \u03bcg\/kg) on gestational day 16. As expected, gestational LPS exposure downregulated 11\u03b2-HSD2 in mice placentas. In vitro, LPS downregulated 11\u03b2-HSD2 in human placental trophoblasts. Additional experiment showed that LPS, which activated NF-\u03baB, suppressed rosiglitazone-induced activation of peroxisome proliferator\u2013activated receptor-\u03b3 (PPAR\u03b3) in mice placentas and human placental trophoblasts. Moreover, NF-\u03baB p65 knockdown and specific NF-\u03baB inhibitor attenuated LPS-induced suppression of PPAR\u03b3 nuclear translocation in human placental trophoblasts. In addition, NF-\u03baB p65 knockdown attenuated LPS-induced downregulation of 11\u03b2-HSD2 in human placental trophoblasts. Mechanically, LPS promoted physical interaction between NF-\u03baB p65 and PPAR\u03b3 in the cytoplasm and nucleus of placental trophoblasts. Finally, pretreatment with rosiglitazone, a PPAR\u03b3 agonist, partially alleviated LPS-induced reduction of fetal weight and crown-rump length. Taken together, these results suggest that LPS downregulates 11\u03b2-HSD2 through suppressing PPAR\u03b3 in placental trophoblasts. Placental 11\u03b2-HSD2 downregulation may contribute partially to LPS-induced fetal IUGR.<\/jats:p>","DOI":"10.4049\/jimmunol.1900132","type":"journal-article","created":{"date-parts":[[2019,7,17]],"date-time":"2019-07-17T14:45:14Z","timestamp":1563374714000},"page":"1198-1207","source":"Crossref","is-referenced-by-count":29,"title":["Lipopolysaccharide Downregulates 11\u03b2-Hydroxysteroid Dehydrogenase 2 Expression through Inhibiting Peroxisome Proliferator\u2013Activated Receptor-\u03b3 in Placental Trophoblasts"],"prefix":"10.1093","volume":"203","author":[{"given":"Lin","family":"Fu","sequence":"first","affiliation":[{"name":"The Second Affiliated Hospital, Anhui Medical University , Hefei 230032 ,","place":["China"]},{"name":"Department of Toxicology, Anhui Medical University , Hefei 230032 ,","place":["China"]},{"name":"Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Anhui Medical University , Hefei 230032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7344-4436","authenticated-orcid":false,"given":"Yuan-Hua","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Anhui Medical University , Hefei 230032 ,","place":["China"]},{"name":"Department of Histology and Embryology, Anhui Medical University , Hefei 230032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-Li","family":"Bo","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Anhui Medical University , Hefei 230032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Ping","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Anhui Medical University , Hefei 230032 ,","place":["China"]},{"name":"Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Anhui Medical University , Hefei 230032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Anhui Medical University , Hefei 230032 ,","place":["China"]},{"name":"Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Anhui Medical University , Hefei 230032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Anhui Medical University , Hefei 230032 ,","place":["China"]},{"name":"Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Anhui Medical University , Hefei 230032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shen","family":"Xu","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital, Anhui Medical University , Hefei 230032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Anhui Medical University , Hefei 230032 ,","place":["China"]},{"name":"Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Anhui Medical University , Hefei 230032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Anhui Medical University , Hefei 230032 ,","place":["China"]},{"name":"Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Anhui Medical University , Hefei 230032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De-Xiang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Anhui Medical University , Hefei 230032 ,","place":["China"]},{"name":"Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Anhui Medical University , Hefei 230032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,9,1]]},"reference":[{"key":"2025030417541858100_r1","doi-asserted-by":"crossref","first-page":"G1","DOI":"10.1152\/ajpgi.00098.2016","article-title":"Gastrointestinal and hepatic mechanisms limiting entry and dissemination of lipopolysaccharide into the systemic circulation","volume":"311","author":"Guerville","year":"2016","journal-title":"Am. 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