TY - JOUR
T1 - Synthetic PreImplantation Factor (sPIF) reduces inflammation and prevents preterm birth
AU - Spinelli, Marialuigia
AU - Boucard, Céline
AU - Nicuolo, Fiorella Di
AU - Haesler, Valerie
AU - Castellani, Roberta
AU - Pontecorvi, Alfredo
AU - Scambia, Giovanni
AU - Granieri, Chiara
AU - Barnea, Eytan R.
AU - Surbek, Daniel
AU - Mueller, Martin
AU - Simone, Nicoletta Di
N1 - Funding Information:
NDS and MM received an unrestricted fund from BioIncept. BioIncept provided sPIF. ERB is CSO of BioIncept. The specific roles of this authors are articulated in the ?author contributions? section. In addition, the following grants helped fund this research: Universita Cattolica del Sacro Cuore (D1 2015: 70201356), Instituto Scientifico Internazionale, Paolo VI Institute, Universit? Cattolica del Sacro Cuore, Rome, Italy to NDS, and University Hospital Bern (2019-00431) to MS and MM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2020 Spinelli et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/6
Y1 - 2020/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85086222781&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85086222781&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0232493
DO - 10.1371/journal.pone.0232493
M3 - Article
C2 - 32511256
AN - SCOPUS:85086222781
VL - 15
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 6
M1 - e0232493
ER -