A pivotal role for the IL-1β and the inflammasome in preterm labor.
Fiche publication
Date publication
février 2024
Journal
Scientific reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GARRIDO Carmen, Pr LIRUSSI Frédéric, Dr WENDREMAIRE Maeva
Tous les auteurs :
Lopez TE, Zhang H, Bouysse E, Neiers F, Ye XY, Garrido C, Wendremaire M, Lirussi F
Lien Pubmed
Résumé
During labor, monocytes infiltrate massively the myometrium and differentiate into macrophages secreting high levels of reactive oxygen species and of pro-inflammatory cytokines (i.e. IL-1β), leading to myometrial contraction. Although IL-1β is clearly implicated in labor, its function and that of the inflammasome complex that cleaves the cytokine in its active form, has never been studied on steps preceding contraction. In this work, we used our model of lipopolysaccharide-induced preterm labor to highlight their role. We demonstrated that IL-1β was secreted by the human myometrium during labor or in presence of infection and was essential for myometrial efficient contractions as its blockage with an IL-1 receptor antagonist (Anakinra) or a neutralizing antibody completely inhibited the induced contractions. We evaluated the implication of the inflammasome on myometrial contractions and differentiation stages of labor onset. We showed that the effects of macrophage-released IL-1β in myometrial cell transactivation were blocked by inhibition of the inflammasome, suggesting that the inflammasome by producing IL-1β was essential in macrophage/myocyte crosstalk during labor. These findings provide novel innovative approaches in the management of preterm labor, specifically the use of an inflammasome inhibitor to block the precursor stages of labor before the acquisition of the contractile phenotype.
Mots clés
Female, Humans, Infant, Newborn, Pregnancy, Cells, Cultured, Cytokines, genetics, Inflammasomes, Interleukin-1beta, genetics, Labor, Obstetric, Myometrium, Obstetric Labor, Premature
Référence
Sci Rep. 2024 02 20;14(1):4234