Rosiglitazone pretreatment protects against lipopolysaccharide-induced fetal demise through inhibiting placental inflammation.

Abstract

Peroxisome proliferator-activated receptor (PPAR)-γ is highly expressed in human and rodent placentas. Nevertheless, its function remains obscure. The present study investigated the effects of rosiglitazone, a PPAR-γ agonist, on LPS-induced fetal death. All pregnant mice except controls were intraperitoneally injected with LPS (150 μg/kg) daily from gestational day (GD)15 to GD17. As expected, maternal LPS injection caused placental inflammation and resulted in 63.6% fetal death in dams that completed the pregnancy. Interestingly, LPS-induced fetal mortality was reduced to 16.0% when pregnant mice were pretreated with RSG. Additional experiment showed that rosiglitazone pretreatment inhibited LPS-induced expressions of tumor necrosis factor (Tnf)-α, interleukin (Il)-1β, Il-6, macrophage inflammatory protein (Mip)-2 and keratinocyte-derived chemokine (Kc) in mouse placenta. Although rosiglitazone had little effect on LPS-evoked elevation of IL-10 in amniotic fluid, it alleviated LPS-evoked release of TNF-α and MIP-2 in amniotic fluid. Further analysis showed that pretreatment with rosiglitazone, which activated placental PPAR-γ signaling, simultaneously suppressed LPS-evoked nuclear factor kappa B (NF-κB) activation and blocked nuclear translocation of NF-κB p65 and p50 subunits in trophoblast giant cells of the labyrinth layer. These results provide a mechanistic explanation for PPAR-γ-mediated anti-inflammatory activity in the placentas. Overall, the present study provides additional evidence for roles of PPAR-γ as an important regulator of placental inflammation.

• Authors: Qing-Li Bo, Yuan-Hua Chen, Zhen Yu, Lin Fu, Yan Zhou, Gui-Bin Zhang, Hua Wang, Zhi-Hui Zhang, De-Xiang Xu
• Journal: Molecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 423 Pg. 51-9 (Mar 05 2016) ISSN: 1872-8057 [Electronic] Ireland
• PMID: 26773728 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Chemokines
• Lipopolysaccharides
• NF-kappa B
• PPAR gamma
• Thiazolidinediones
• Rosiglitazone

Topics

• Active Transport, Cell Nucleus
• Animals
• Anti-Inflammatory Agents (administration & dosage)
• Chemokines (blood)
• Drug Evaluation, Preclinical
• Female
• Fetal Death (prevention & control)
• Lipopolysaccharides (pharmacology)
• Male
• Mice, Inbred ICR
• NF-kappa B (metabolism)
• PPAR gamma (metabolism)
• Placenta (drug effects, immunology, metabolism)
• Pregnancy
• Rosiglitazone
• Signal Transduction
• Thiazolidinediones (administration & dosage)