Synthetic PreImplantation Factor (PIF) prevents fetal loss by modulating LPS induced inflammatory response

Nicoletta Di Simone, Francesco Ria, Giovanni Scambia, Riccardo Marana, Roberta Castellani, Manuela Veglia, Daniel Surbek, Eytan Barnea, Martin Mueller

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

13 Citazioni (Scopus)

Abstract

Maternal control of inflammation is essential during pregnancy and an exaggerated response is one of the underlying causes of fetal loss. Inflammatory response is mediated by multiple factors and Toll-like receptors (TLRs) are central. Activation of TLRs results in NALP-3 mediated assembly of apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1 into the inflammasome and production of pro-inflammatory cytokines IL-1β and IL-18. Given that preventing measures are lacking, we investigated PreImplantation Factor (PIF) as therapeutic option as PIF modulates Inflammation in pregnancy. Additionally, synthetic PIF (PIF analog) protects against multiple immune disorders. We used a LPS induced murine model of fetal loss and synthetic PIF reduced this fetal loss and increased the embryo weight significantly. We detected increased PIF expression in the placentae after LPS insult. The LPS induced serum and placenta cytokines were abolished by synthetic PIF treatment and importantly synthetic PIF modulated key members of inflammasome complex NALP-3, ASC, and caspase-1 as well. In conclusion our results indicate that synthetic PIF protects against LPS induced fetal loss, likely through modulation of inflammatory response especially the inflammasome complex. Given that synthetic PIF is currently tested in autoimmune diseases of non-pregnant subjects (clinicaltrials.gov, NCT02239562), therapeutic approach during pregnancy can be envisioned.
Lingua originaleEnglish
pagine (da-a)1-16
Numero di pagine16
RivistaPLoS One
DOI
Stato di pubblicazionePubblicato - 2017

Keywords

  • infection, inflammation
  • pre- implantation factor ( PIF ), fetal loss, LPS

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