title: Vitamin D3 inhibits lipopolysaccharide-induced placental inflammation through reinforcing interaction between vitamin D receptor and nuclear factor kappa B p65 subunit.
abstract: It is increasingly recognized that vitamin D3 (VitD3) has an anti-inflammatory activity. The present study investigated the effects of maternal VitD3 supplementation during pregnancy on LPS-induced placental inflammation and fetal intrauterine growth restriction (IUGR). All pregnant mice except controls were intraperitoneally injected with LPS (100 μg/kg) daily from gestational day (GD)15-17. In VitD3 + LPS group, pregnant mice were orally administered with VitD3 (25 μg/kg) before LPS injection. As expected, maternal LPS exposure caused placental inflammation and fetal IUGR. Interestingly, pretreatment with VitD3 repressed placental inflammation and protected against LPS-induced fetal IUGR. Further analysis showed that pretreatment with VitD3, which activated placental vitamin D receptor (VDR) signaling, specifically suppressed LPS-induced activation of nuclear factor kappa B (NF-κB) and significantly blocked nuclear translocation of NF-κB p65 subunit in trophoblast gaint cells of the labyrinth layer. Conversely, LPS, which activated placental NF-κB signaling, suppressed placental VDR activation and its target gene expression. Moreover, VitD3 reinforced physical interaction between placental VDR and NF-κB p65 subunit. The further study demonstrates that VitD3 inhibits placental NF-κB signaling in VDR-dependent manner. These results provide a mechanistic explanation for VitD3-mediated anti-inflammatory activity. Overall, the present study provides evidence for roles of VDR as a key regulator of placental inflammation.
authors.affiliation: 1] School of Public Health, Anhui Medical University, Hefei, China [2] Anhui Provincial Key Laboratory of Population Health &Aristogenics, Anhui Medical University, Hefei, China [3] School of Basic Medical Science, Anhui Medical University, Hefei, 230032, China.
authors.forename: Yuan-Hua
authors.initials: YH
authors.lastname: Chen
authors.affiliation: 1] School of Public Health, Anhui Medical University, Hefei, China [2] Anhui Provincial Key Laboratory of Population Health &Aristogenics, Anhui Medical University, Hefei, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yu
authors.affiliation: School of Public Health, Anhui Medical University, Hefei, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Fu
authors.affiliation: 1] School of Public Health, Anhui Medical University, Hefei, China [2] Anhui Provincial Key Laboratory of Population Health &Aristogenics, Anhui Medical University, Hefei, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: School of Public Health, Anhui Medical University, Hefei, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Chen
authors.affiliation: 1] School of Public Health, Anhui Medical University, Hefei, China [2] Anhui Provincial Key Laboratory of Population Health &Aristogenics, Anhui Medical University, Hefei, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: School of Basic Medical Science, Anhui Medical University, Hefei, 230032, China.
authors.forename: Zheng-Mei
authors.initials: ZM
authors.lastname: Lv
authors.affiliation: 1] School of Public Health, Anhui Medical University, Hefei, China [2] Anhui Provincial Key Laboratory of Population Health &Aristogenics, Anhui Medical University, Hefei, China.
authors.forename: De-Xiang
authors.initials: DX
authors.lastname: Xu
mesh_terms: D000818:Animals; D002762:Cholecalciferol / Q000494:pharmacology*; D005260:Female; D005317:Fetal Growth Retardation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010920:Placenta / Q000378:metabolism / Q000473:pathology; D010922:Placenta Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D018167:Receptors, Calcitriol / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D051996:Transcription Factor RelA / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D018167:Receptors, Calcitriol; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D002762:Cholecalciferol