OBJECTIVES: Maternal magnesium sulfate (MgSO4) administration exerts anti-inflammatory and fetal neuroprotective effects. Based on the link between placental inflammation and fetal immune responses, we examined the effect of MgSO4 on LPS-induced inflammation at the maternal-fetal interface. STUDY DESIGN: In vivo model: Pregnant rats (GD19) were injected intraperitoneally with saline, LPS, or MgSO4 plus LPS (n = 6 per group). Rats were euthanized; placentas were assayed for CCL2, IL6, and TNFα and placentas were screened for gene expression. Ex vivo model: Human placental cultures were treated with vehicle, LPS, or MgSO4 plus LPS. Supernatants were assayed for CCL2, IL6, and TNFα. In addition, placental cultures were analyzed for inflammation-related gene expression and NFκ B activation. RESULTS: In vivo model: Maternal LPS administration resulted in pro-inflammatory mediator production within the placenta; maternal MgSO4 treatment significantly attenuated LPS-induced inflammation. Several placental transcripts (APOE, CCL4, CXCL1, and NFκBIZ) differentially expressed following maternal LPS challenge were counter-regulated by MgSO4 treatment. Ex vivo model: LPS promoted human placental inflammation and MgSO4 significantly reduced inflammation induced by LPS. MgSO4 treatment of human placental explants significantly reversed the expression of numerous genes sensitive to LPS regulation and suppressed LPS-induced NFκB activation. CONCLUSIONS: MgSO4 administration inhibited placental inflammation during LPS-mediated maternal infection. Several placental inflammatory genes whose expression was regulated by LPS were reversed by MgSO4 treatment. Our data support the hypothesis that MgSO4 attenuates excessive inflammation at the maternal-fetal interface, which when uncontrolled may compromise neonatal health, including neurologic outcomes.
OBJECTIVES: Maternal magnesium sulfate (MgSO4) administration exerts anti-inflammatory and fetal neuroprotective effects. Based on the link between placental inflammation and fetal immune responses, we examined the effect of MgSO4 on LPS-induced inflammation at the maternal-fetal interface. STUDY DESIGN: In vivo model: Pregnant rats (GD19) were injected intraperitoneally with saline, LPS, or MgSO4 plus LPS (n = 6 per group). Rats were euthanized; placentas were assayed for CCL2, IL6, and TNFα and placentas were screened for gene expression. Ex vivo model: Human placental cultures were treated with vehicle, LPS, or MgSO4 plus LPS. Supernatants were assayed for CCL2, IL6, and TNFα. In addition, placental cultures were analyzed for inflammation-related gene expression and NFκ B activation. RESULTS: In vivo model: Maternal LPS administration resulted in pro-inflammatory mediator production within the placenta; maternal MgSO4 treatment significantly attenuated LPS-induced inflammation. Several placental transcripts (APOE, CCL4, CXCL1, and NFκBIZ) differentially expressed following maternal LPS challenge were counter-regulated by MgSO4 treatment. Ex vivo model: LPS promoted human placental inflammation and MgSO4 significantly reduced inflammation induced by LPS. MgSO4 treatment of human placental explants significantly reversed the expression of numerous genes sensitive to LPS regulation and suppressed LPS-induced NFκB activation. CONCLUSIONS:MgSO4 administration inhibited placental inflammation during LPS-mediated maternal infection. Several placental inflammatory genes whose expression was regulated by LPS were reversed by MgSO4 treatment. Our data support the hypothesis that MgSO4 attenuates excessive inflammation at the maternal-fetal interface, which when uncontrolled may compromise neonatal health, including neurologic outcomes.
Authors: Alan Leviton; Robert M Joseph; Elizabeth N Allred; T Michael O'Shea; H Gerry Taylor; Karl K C Kuban Journal: J Child Neurol Date: 2018-01-11 Impact factor: 1.987
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Authors: Wei Qiao; Karen H M Wong; Jie Shen; Wenhao Wang; Jun Wu; Jinhua Li; Zhengjie Lin; Zetao Chen; Jukka P Matinlinna; Yufeng Zheng; Shuilin Wu; Xuanyong Liu; Keng Po Lai; Zhuofan Chen; Yun Wah Lam; Kenneth M C Cheung; Kelvin W K Yeung Journal: Nat Commun Date: 2021-05-17 Impact factor: 14.919