Synthetic PreImplantation Factor (sPIF) reduces inflammation and prevents preterm birth

Marialuigia Spinelli, Céline Boucard, Fiorella Di Nicuolo, Valerie Haesler, Roberta Castellani, Alfredo Pontecorvi, Giovanni Scambia, Chiara Granieri, Eytan R. Barnea, Daniel Surbek, Martin Mueller, Nicoletta Di Simone

Research output: Contribution to journalArticlepeer-review

Abstract

Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality and spontaneous PTB is a major contributor. The preceding inflammation/infection contributes not only to spontaneous PTB but is associated with neonatal morbidities including impaired brain development. Therefore, control of exaggerated immune response during pregnancy is an attractive strategy. A potential candidate is synthetic PreImplantation Factor (sPIF) as sPIF prevents inflammatory induced fetal loss and has neuroprotective properties. Here, we tested maternal sPIF prophylaxis in pregnant mice subjected to a lipopolysaccharides (LPS) insult, which results in PTB. Additionally, we evaluated sPIF effects in placental and microglial cell lines. Maternal sPIF application reduced the LPS induced PTB rate significantly. Consequently, sPIF reduced microglial activation (Iba-1 positive cells) and preserved neuronal migration (Cux-2 positive cells) in fetal brains. In fetal brain lysates sPIF decreased IL-6 and INFγ concentrations. In-vitro, sPIF reduced Iba1 and TNFα expression in microglial cells and reduced the expression of pro-apoptotic (Bad and Bax) and inflammatory (IL-6 and NLRP4) genes in placental cell lines. Together, maternal sPIF prophylaxis prevents PTB in part by controlling exaggerated immune response. Given the sPIF‘FDA Fast Track approval in non-pregnant subjects, we envision sPIF therapy in pregnancy.

Original languageEnglish
Article numbere0232493
JournalPLoS One
Volume15
Issue number6
DOIs
Publication statusPublished - Jun 2020

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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