Damage-associated molecular patterns (DAMPs) in preterm labor with intact membranes and preterm PROM: a study of the alarmin HMGB1

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dc.contributor.authorRomero, Roberto
dc.contributor.authorChaiworapongsa, Tinnakorn
dc.contributor.authorSavasan, Zeynep Alpay
dc.contributor.authorXu, Yi
dc.contributor.authorHussein, Youssef
dc.contributor.authorDong, Zhong
dc.contributor.authorPedro Kusanovic, Juan
dc.contributor.authorKim, Chong Jai
dc.contributor.authorHassan, Sonia S.
dc.date.accessioned2024-01-10T13:12:08Z
dc.date.available2024-01-10T13:12:08Z
dc.date.issued2011
dc.description.abstractObjective: Preterm parturition is a syndrome caused by multiple etiologies. Although intra-amniotic infection is causally linked with intrauterine inflammation and the onset of preterm labor, other patients have preterm labor in the absence of demonstrable infection. It is now clear that inflammation may be elicited by activation of the Damage-Associated Molecular Patterns (DAMPs), which include pathogen-associated molecular patterns (PAMPs) as well as "alarmins" (endogenous molecules that signal tissue and cellular damage). A prototypic alarmin is high-mobility group box 1 (HMGB1) protein, capable of inducing inflammation and tissue repair when it reaches the extracellular environment. HMGB1 is a late mediator of sepsis, and blockade of HMGB1 activity reduces mortality in an animal model of endotoxemia, even if administered late during the course of the disorder. The objectives of this study were to: (1) determine whether intra-amniotic infection/inflammation (IAI) is associated with changes in amniotic fluid concentrations of HMGB1; and (2) localize immunoreactivity of HMGB1 in the fetal membranes and umbilical cord of patients with chorioamnionitis. Methods: Amniotic fluid samples were collected from the following groups: (1) preterm labor with intact membranes (PTL) with (n = 42) and without IAI (n = 84); and (2) preterm prelabor rupture of membranes (PROM) with (n = 38) and without IAI (n = 35). IAI was defined as either a positive amniotic fluid culture or amniotic fluid concentration of interleukin-6 (IL-6) >= 2.6 ng/mL. HMGB1 concentrations in amniotic fluid were determined by ELISA. Immunofluorescence staining for HMGB1 was performed in the fetal membranes and umbilical cord of pregnancies with acute chorioamnionitis. Results: (1) Amniotic fluid HMGB1 concentrations were higher in patients with IAI than in those without IAI in both the PTL and preterm PROM groups (PTL IAI: median 3.1 ng/mL vs. without IAI; median 0.98 ng/mL; p < 0.001; and preterm PROM with IAI median 7.3 ng/mL vs. without IAI median 2.6 ng/mL; p = 0.002); (2) patients with preterm PROM without IAI had a higher median amniotic fluid HMGB1 concentration than those with PTL and intact membranes without IAI (p < 0.001); and (3) HMGB1 was immunolocalized to amnion epithelial cells and stromal cells in the Wharton's jelly (prominent in the nuclei and cytoplasm). Myofibroblasts and macrophages of the chorioamniotic connective tissue layer and infiltrating neutrophils showed diffuse cytoplasmic HMGB1 immunoreactivity. Conclusions: (1) intra-amniotic infection/inflammation is associated with elevated amniotic fluid HMGB1 concentrations regardless of membrane status; (2) preterm PROM was associated with a higher amniotic fluid HMGB1 concentration than PTL with intact membranes, suggesting that rupture of membranes is associated with an elevation of alarmins; (3) immunoreactive HMGB1 was localized to amnion epithelial cells, Wharton's jelly and cells involved in the innate immune response; and (4) we propose that HMGB1 released from stress or injured cells into amniotic fluid may be responsible, in part, for intra-amniotic inflammation due to non-microbial insults.
dc.description.funderPerinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS
dc.description.funderEUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
dc.description.funderEUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT
dc.fechaingreso.objetodigital2024-05-23
dc.format.extent12 páginas
dc.fuente.origenWOS
dc.identifier.doi10.3109/14767058.2011.591460
dc.identifier.eissn1476-4954
dc.identifier.issn1476-7058
dc.identifier.pubmedidMEDLINE:21958433
dc.identifier.urihttps://doi.org/10.3109/14767058.2011.591460
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/78145
dc.identifier.wosidWOS:000296778800007
dc.information.autorucMedicina;Kusanovic J;S/I;1008900
dc.issue.numero12
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final1455
dc.pagina.inicio1444
dc.publisherTAYLOR & FRANCIS LTD
dc.revistaJOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
dc.rightsacceso restringido
dc.subjectpreterm prelabor rupture of membranes
dc.subjectintra-amniotic infection
dc.subjectintra-amniotic inflammation
dc.subjectchorioamnionitis
dc.subjectalarmin
dc.subjectRAGE
dc.subjectamniotic fluid
dc.subjectdanger signal
dc.subjectMOBILITY GROUP BOX-1
dc.subjectPOLYMERASE-CHAIN-REACTION
dc.subjectAMNIOTIC-FLUID CONCENTRATIONS
dc.subjectTUMOR-NECROSIS-FACTOR
dc.subjectPREMATURE RUPTURE
dc.subjectINTRAAMNIOTIC INFECTION
dc.subjectUREAPLASMA-UREALYTICUM
dc.subjectCLINICAL-SIGNIFICANCE
dc.subjectPROINFLAMMATORY ACTIVITY
dc.subjectMICROBIAL INVASION
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.titleDamage-associated molecular patterns (DAMPs) in preterm labor with intact membranes and preterm PROM: a study of the alarmin HMGB1
dc.typeartículo
dc.volumen24
sipa.codpersvinculados1008900
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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