Placental regulation of inflammation and hypoxia after TNF-alphaiInfusion in mice

Gabriele A Bobek, Laura Surmon, Katrina M Mirabito, Angela Makris, Annemarie Hennessy

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33 Citations (Scopus)


PROBLEM: Increased levels of inflammatory cytokines are demonstrated in the serum of women with pre-eclampsia. TNF-alpha infusion in animal models induces proteinuric hypertension similar to human pre-eclampsia. The effect of TNF-alpha 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-alpha 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-1alpha) were examined. RESULTS: TNF-alpha infusion resulted in maternal hypertension and proteinuria. Molecular changes in the placenta involved upregulation of TLR-3, TLR-4 and HIF-1alpha. Serum levels of sFlt-1 were high in pregnant animals, but not further upregulated by TNF-alpha infusion. CONCLUSION: A role for maladaptive regulation of TLR and HIF-1alpha induced by an imbalance in inflammatory cytokines is implicated in the pathogenesis of pre-eclampsia.
Original languageEnglish
Pages (from-to)407 - 418
Number of pages12
JournalAmerican Journal of Reproductive Immunology
Issue number5
Publication statusPublished - 2015

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