A key role for NLRP3 signaling in preterm labor and birth driven by the alarmin S100B

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dc.contributor.authorGalaz, Jose
dc.contributor.authorMotomura, Kenichiro
dc.contributor.authorRomero, Roberto
dc.contributor.authorLiu, Zhenjie
dc.contributor.authorGarcia-Flores, Valeria
dc.contributor.authorTao, Li
dc.contributor.authorXu, Yi
dc.contributor.authorDone, Bogdan
dc.contributor.authorArenas-Hernandez, Marcia
dc.contributor.authorKanninen, Tomi
dc.contributor.authorFarias-Jofre, Marcelo
dc.contributor.authorMiller, Derek
dc.contributor.authorTarca, Adi L.
dc.contributor.authorGomez-Lopez, Nardhy
dc.date.accessioned2025-01-20T20:07:35Z
dc.date.available2025-01-20T20:07:35Z
dc.date.issued2023
dc.description.abstractPreterm birth remains the leading cause of neonatal morbidity and mortality worldwide. A substantial number of spontaneous preterm births occur in the context of sterile intra-amniotic inflammation, a condition that has been mechanistically proven to be triggered by alarmins. However, sterile intra-amniotic inflammation still lacks treatment. The NLRP3 inflammasome has been implicated in sterile intra-amniotic inflammation; yet, its underlying mechanisms, as well as the maternal and fetal contributions to this signaling pathway, are unclear. Herein, by utilizing a translational and clinically relevant model of alarmin-induced preterm labor and birth in Nlrp3-/- mice, we investigated the role of NLRP3 signaling by using imaging and molecular biology approaches. Nlrp3 deficiency abrogated preterm birth and the resulting neonatal mortality induced by the alarmin S100B by impeding the premature activation of the common pathway of labor as well as by dampening intra-amniotic and fetal inflammation. Moreover, Nlrp3 deficiency altered leukocyte infiltration and functionality in the uterus and decidua. Last, embryo transfer revealed that maternal and fetal Nlrp3 signaling contribute to alarmin-induced preterm birth and neonatal mortality, further strengthening the concept that both individuals participate in the complex process of preterm parturition. These findings provide novel insights into sterile intra-amniotic inflammation, a common etiology of preterm labor and birth, suggesting that the adverse perinatal outcomes resulting from prematurity can be prevented by targeting NLRP3 signaling.
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.trsl.2023.04.004
dc.identifier.eissn1878-1810
dc.identifier.issn1931-5244
dc.identifier.urihttps://doi.org/10.1016/j.trsl.2023.04.004
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/91822
dc.identifier.wosidWOS:001048415700001
dc.language.isoen
dc.pagina.final61
dc.pagina.inicio46
dc.revistaTranslational research
dc.rightsacceso restringido
dc.subjectsterile intra-amniotic inflammation
dc.subjectinflammasome
dc.subjectprematurity
dc.subjectfetus
dc.subjectneonate
dc.subjectpreterm birth
dc.subjectparturition
dc.subject.ods05 Gender Equality
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa05 Igualdad de género
dc.subject.odspa03 Salud y bienestar
dc.titleA key role for NLRP3 signaling in preterm labor and birth driven by the alarmin S100B
dc.typeartículo
dc.volumen259
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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