Secretory phospholipase A2 expression and activity in preterm clinical chorioamnionitis with fetal involvement

Author:

De Luca Daniele12ORCID,Foligno Silvia1,Autilio Chiara3ORCID,Vivanti Alexandre4,Vandekerckhove Melanie4,Martinovic Jelena5,Raschetti Roberto1,Guillot Loïc6ORCID,Touqui Lhousseine67

Affiliation:

1. Division of Pediatrics and Neonatal Critical Care, “Antoine Béclère” Medical Centre, Paris Saclay University Hospitals, APHP, Paris, France

2. Physiopathology and Therapeutic Innovation Unit-INSERM U999, Paris Saclay University, Paris, France

3. Department of Biochemistry and Molecular Biology, Faculty of Biology, and Research Institut-Hospital “12 de Octubre,” Complutense University, Madrid, Spain

4. Division of Obstetrics and Gynecology, “Antoine Béclère” Hospital, Paris Saclay University Hospitals, APHP, Paris, France

5. Unit of Fetopathology, “Antoine Béclère” Hospital, Paris Saclay University Hospitals, APHP, Paris, France

6. INSERM UMR-S938, Centre de Recherche Saint-Antoine (CRSA), Sorbonne Université, Paris, France

7. Equipe Mucoviscidose et Bronchopathies Chroniques, Département Santé Globale, Institut Pasteur, Paris, France

Abstract

Secretory phospholipase A2 (sPLA2) regulates the first step of inflammatory cascade and is involved in several pathological processes. sPLA2 also plays a role in preterm labor and parturition, since they are triggered by inflammatory mediators such as prostaglandins. Interestingly, chorioamnionitis (i.e., the presence of intrauterine inflammation) is also often associated with preterm birth. We aimed to verify if chorioamnionitis with fetal involvement modifies sPLA2 activity and expression profile in mothers and neonates delivered prematurely. We collected maternal plasma and amniotic fluid, as well as bronchoalveolar lavage fluid from preterm neonates born to mothers with or without clinical chorioamnionitis with fetal involvement. We measured concentrations of sPLA2 subtype-IIA and -IB, total enzyme activity, and proteins. Urea ratio was used to obtain epithelial lining fluid concentrations. Enzyme activity measured in maternal plasma ( P < 0.001) and amniotic fluid ( P < 0.001) was higher in chorioamnionitis cases than in controls. This was mainly due to the increased production of sPLA2-IIA, as the subtype -IB was present in a smaller amount and was similar between the two groups; sPLA2-IIA was increased in epithelial lining fluid ( P = 0.045) or increased, although without statistical significance, in maternal plasma ( P = 0.06) and amniotic fluid ( P = 0.08) of chorioamnionitis cases. Cytokines that are known to increase sPLA2-IIA expression (TNF-α and IL-1β) or whose expression was increased by sPLA2-IIA (IL-8) were higher in histologically confirmed chorioamnionitis [TNF-α ( P = 0.028), IL-1β ( P < 0.001), and IL-8 ( P = 0.038)]. These data represent the basis for future studies on sPLA2-IIA inhibition to prevent deleterious consequences of chorioamnionitis and preterm birth.

Funder

Association for Research and Development in Neonatology

Publisher

American Physiological Society

Subject

Cell Biology,Physiology (medical),Pulmonary and Respiratory Medicine,Physiology

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