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: Yuan-Hua Chen, Zhen Yu, Lin Fu, Hua Wang, Xue Chen, Cheng Zhang, Zheng-Mei Lv, De-Xiang Xu
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 10871 (Jun 12 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 26065916 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lipopolysaccharides
• Receptors, Calcitriol
• Rela protein, mouse
• Transcription Factor RelA
• Cholecalciferol

Topics

• Animals
• Cholecalciferol (pharmacology)
• Female
• Fetal Growth Retardation (chemically induced, drug therapy, metabolism, pathology)
• Inflammation (chemically induced, drug therapy, metabolism, pathology)
• Lipopolysaccharides (toxicity)
• Male
• Mice
• Mice, Inbred ICR
• Placenta (metabolism, pathology)
• Placenta Diseases (chemically induced, drug therapy, metabolism, pathology)
• Pregnancy
• Receptors, Calcitriol (metabolism)
• Signal Transduction (drug effects)
• Transcription Factor RelA (metabolism)