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  • Title: Placental Regulation of Inflammation and Hypoxia after TNF-α Infusion in Mice.
    Author: Bobek G, Surmon L, Mirabito KM, Makris A, Hennessy A.
    Journal: Am J Reprod Immunol; 2015 Nov; 74(5):407-18. PubMed ID: 26220019.
    Abstract:
    PROBLEM: Increased levels of inflammatory cytokines are demonstrated in the serum of women with pre-eclampsia. TNF-α infusion in animal models induces proteinuric hypertension similar to human pre-eclampsia. The effect of TNF-α on regulation of the immune and hypoxic pathways in the developing placenta and their relationship with experimental pre-eclampsia remains unexamined. METHOD OF STUDY: TNF-α was infused into pregnant mice, and the effects on maternal hypertension, proteinuria, circulating levels of sFlt-1 and corresponding placental changes in molecules responding to inflammation (TLR-3 and TLR-4) and hypoxia (HIF-1α) were examined. RESULTS: TNF-α infusion resulted in maternal hypertension and proteinuria. Molecular changes in the placenta involved upregulation of TLR-3, TLR-4 and HIF-1α. Serum levels of sFlt-1 were high in pregnant animals, but not further upregulated by TNF-α infusion. CONCLUSION: A role for maladaptive regulation of TLR and HIF-1α induced by an imbalance in inflammatory cytokines is implicated in the pathogenesis of pre-eclampsia.
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