2024
Predictors of Inflammation-Mediated Preterm Birth
Geroges H, Norwitz E, Abrahams V. Predictors of Inflammation-Mediated Preterm Birth. Physiology 2024 PMID: 39106300, DOI: 10.1152/physiol.00022.2024.Peer-Reviewed Original ResearchAntiphospholipid-exposed trophoblast-derived extracellular vesicles express elevated levels of TLR7/8-activating microRNAs and induce endometrial endothelial activation, in part, through TLR7
Coenen C, Hidalgo T, Lynn T, Jones D, Salmon J, Chamley L, Abrahams V. Antiphospholipid-exposed trophoblast-derived extracellular vesicles express elevated levels of TLR7/8-activating microRNAs and induce endometrial endothelial activation, in part, through TLR7. Journal Of Reproductive Immunology 2024, 164: 104255. PMID: 38797133, DOI: 10.1016/j.jri.2024.104255.Peer-Reviewed Original ResearchHuman endometrial endothelial cellsObstetric antiphospholipid syndromeToll-like receptor 4MiR-146a-3pMaternal-fetal interfaceAntiphospholipid syndromeIL-8 responseEndometrial endothelial cellsTrophoblast cellsExtracellular vesiclesElevated levels of IL-8IL-8Endothelial cellsLevels of IL-8Activation of Toll-like receptor 4Downstream of toll-like receptor 4Exposure to aPLElevated levelsExtravillous trophoblast cellsHuman trophoblast cellsInsufficient placentationTrophoblast-derived extracellular vesiclesAntiphospholipid antibodiesMaternal vasculaturePlacental trophoblastsTLR8‐activating miR‐146a‐3p is an intermediate signal contributing to fetal membrane inflammation in response to bacterial LPS
Georges H, Cassin C, Tong M, Abrahams V. TLR8‐activating miR‐146a‐3p is an intermediate signal contributing to fetal membrane inflammation in response to bacterial LPS. Immunology 2024, 172: 577-587. PMID: 38631842, PMCID: PMC11223956, DOI: 10.1111/imm.13794.Peer-Reviewed Original ResearchMiR-146a-3pPreterm birthFetal membranesToll-like receptorsExpression of miR-146a-3pLipopolysaccharide exposureMouse model of pregnancyIL-8Response to bacterial LPSAssociated with chorioamnionitisFetal membrane inflammationHuman FM explantsMouse fetal membranesInduced preterm birthBacterial lipopolysaccharideMaternal-fetal interfaceDanger signalsWild-type miceIn vivo mouse modelModel of pregnancyInterleukin (IL)-8Pro-inflammatory roleResponse to bacterial lipopolysaccharideAssociated with elevated levelsResponse to LPS
2023
Decidualization dampens toll-like receptor mediated inflammatory responses in human endometrial stromal cells by upregulating IκBα
Tong M, Scott J, Whirledge S, Abrahams V. Decidualization dampens toll-like receptor mediated inflammatory responses in human endometrial stromal cells by upregulating IκBα. Journal Of Reproductive Immunology 2023, 159: 103988. PMID: 37451159, PMCID: PMC10530124, DOI: 10.1016/j.jri.2023.103988.Peer-Reviewed Original ResearchConceptsEndometrial stromal cellsInflammatory responseStromal cellsHuman endometrial stromal cellsToll-like receptor signalingSex hormone levelsMenstrual cycle stageToll-like receptorsImmune response changesViral double-stranded RNAHuman EnSCsEndometrial responseProinflammatory cytokinesSuccessful pregnancyMenstrual cycleHuman endometriumHormone levelsMajor cell typesImmune responseNFκB p65Viral infectionDecidualizationBacterial lipopolysaccharideReceptor signalingBacterial componentsEndometrial responses to bacterial and viral infection: a scoping review.
Lindsay C, Potter J, Grimshaw A, Abrahams V, Tong M. Endometrial responses to bacterial and viral infection: a scoping review. Human Reproduction Update 2023, 29: 675-693. PMID: 37290428, PMCID: PMC10477945, DOI: 10.1093/humupd/dmad013.Peer-Reviewed Original ResearchConceptsEndometrial responseViral infectionUterus/endometriumFull-text studiesInnate immune sensingInnate immune responseFree-text termsEmbase/MedlineIntrauterine infectionObstetric complicationsEndometrial productionCochrane LibraryFuture studiesImplantation failureNeisseria gonorrheaImmune cellsMost infectionsImmune responseUterine functionChlamydia trachomatisAnimal modelsImmune sensingEndometriumZika virusMajority of studiesCell-free fetal DNA impairs trophoblast migration in a TLR9-dependent manner and can be reversed by hydroxychloroquine
León-Martínez D, Lynn T, Abrahams V. Cell-free fetal DNA impairs trophoblast migration in a TLR9-dependent manner and can be reversed by hydroxychloroquine. Journal Of Reproductive Immunology 2023, 157: 103945. PMID: 37062109, DOI: 10.1016/j.jri.2023.103945.Peer-Reviewed Original ResearchConceptsToll-like receptor 9Aspirin-triggered lipoxinsODN 2216Pathogenesis of preeclampsiaTLR9-dependent mannerNovel therapeutic approachesTrophoblast cell modelReceptor 9CpG oligodeoxynucleotideTLR9 inhibitorPlacental functionTherapeutic approachesCell-free fetal DNACpG motifsTherapeutic agentsHCQPreeclampsiaHydroxychloroquineFetal DNACell viabilityCffDNAMolecular underpinningsCell modelInhibitionASA
2022
Distinct non‐coding RNA cargo of extracellular vesicles from M1 and M2 human primary macrophages
Pantazi P, Clements T, Venø M, Abrahams V, Holder B. Distinct non‐coding RNA cargo of extracellular vesicles from M1 and M2 human primary macrophages. Journal Of Extracellular Vesicles 2022, 11: 12293. PMID: 36544271, PMCID: PMC9772496, DOI: 10.1002/jev2.12293.Peer-Reviewed Original ResearchConceptsNon-coding RNAsSmall non-coding RNAsY RNA fragmentsTRNA fragmentsRNA cargoExtracellular vesiclesFull-length tRNASmall RNA sequencingPrimary macrophagesSmall RNA cargoHigh relative abundanceHuman primary macrophagesRNA sequencingEnrichment analysisGene targetsGene expressionFirst comprehensive analysisSignaling pathwaysFunctional cargoRelative abundanceLow abundancePutative roleRNASnoRNAsInflammatory signaling pathwaysThe serotonin reuptake inhibitor fluoxetine induces human fetal membrane sterile inflammation through p38 MAPK activation
Fabrizio V, Lindsay C, Wilcox M, Hong S, Lynn T, Norwitz E, Yonkers K, Abrahams V. The serotonin reuptake inhibitor fluoxetine induces human fetal membrane sterile inflammation through p38 MAPK activation. Journal Of Reproductive Immunology 2022, 155: 103786. PMID: 36528909, PMCID: PMC9851981, DOI: 10.1016/j.jri.2022.103786.Peer-Reviewed Original ResearchMeSH KeywordsAntidepressive AgentsExtraembryonic MembranesFemaleFetal Membranes, Premature RuptureFluoxetineHumansHydroxymethylglutaryl-CoA Reductase InhibitorsInfant, NewbornInflammationInterleukin-6P38 Mitogen-Activated Protein KinasesPregnancyPremature BirthSelective Serotonin Reuptake InhibitorsConceptsSerotonin reuptake inhibitorsP38 MAPK activitySerotonin reuptake inhibitor fluoxetineSubsequent preterm birthFirst-line therapyPreterm premature ruptureReuptake inhibitor fluoxetineInflammatory IL-6Normal term deliveryIL-6 productionIL-6 secretionFetal membrane inflammationUnexposed womenAntidepressant treatmentLine therapyPreterm birthAntidepressant useReuptake inhibitorsTerm deliveryMembrane inflammationPremature ruptureIL-6SRI useSterile inflammationP38 MAPK pathwayPlacental macrophage responses to viral and bacterial ligands and the influence of fetal sex
Pantazi P, Kaforou M, Tang Z, Abrahams V, McArdle A, Guller S, Holder B. Placental macrophage responses to viral and bacterial ligands and the influence of fetal sex. IScience 2022, 25: 105653. PMID: 36505933, PMCID: PMC9732417, DOI: 10.1016/j.isci.2022.105653.Peer-Reviewed Original ResearchPathogen-associated molecular patternsViral pathogen-associated molecular patternsHofbauer cellsFetal sexMajor histocompatibility complex class IAdverse pregnancy outcomesHistocompatibility complex class IToll-like receptorsComplex class ISex-dependent responseInfectious triggerPregnancy outcomesPlacental macrophagesVertical pathogen transmissionViral infectionLipid metabolismMacrophage responseBacterial ligandsProtein expression changesClass IMolecular patternsPlacentaMacrophagesCytoskeleton organizationQuantitative proteomicsEditorial: Translational Virology in Pregnancy
Waldorf K, Abrahams V. Editorial: Translational Virology in Pregnancy. Frontiers In Virology 2022, 2: 908471. PMID: 36313916, PMCID: PMC9611285, DOI: 10.3389/fviro.2022.908471.Peer-Reviewed Original Research
2019
Lipopolysaccharide-Stimulated Human Fetal Membranes Induce Neutrophil Activation and Release of Vital Neutrophil Extracellular Traps.
Tong M, Potter JA, Mor G, Abrahams VM. Lipopolysaccharide-Stimulated Human Fetal Membranes Induce Neutrophil Activation and Release of Vital Neutrophil Extracellular Traps. The Journal Of Immunology 2019, 203: 500-510. PMID: 31167775, PMCID: PMC6616008, DOI: 10.4049/jimmunol.1900262.Peer-Reviewed Original ResearchConceptsNeutrophil extracellular trapsNeutrophil recruitmentFetal membranesReactive oxygen species productionPreterm birthExtracellular trapsOxygen species productionCytokine/chemokine secretionChemokine/cytokine productionMajor risk factorSpecies productionBacterial LPS stimulationNeutrophil infiltrationProinflammatory factorsFetal interfaceChemokine secretionNeonatal mortalityCytokine productionNeutrophil activationRisk factorsTissue injuryNeutrophil viabilityLPS stimulationEx vivoNET formation
2018
Role of NOD2 in antiphospholipid antibody-induced and bacterial MDP amplification of trophoblast inflammation
Mulla MJ, Pasternak MC, Salmon JE, Chamley LW, Abrahams VM. Role of NOD2 in antiphospholipid antibody-induced and bacterial MDP amplification of trophoblast inflammation. Journal Of Autoimmunity 2018, 98: 103-112. PMID: 30594350, DOI: 10.1016/j.jaut.2018.12.003.Peer-Reviewed Original ResearchConceptsMuramyl dipeptideAbsence of aPLAnti-angiogenic profileNovel danger signalPresence of aPLRole of NOD2IL-1β expressionMaternal-fetal interfaceActivation of NOD2IL-1β productionBacterial muramyl dipeptideAntiphospholipid antibodiesCommon bacterial componentsPregnancy complicationsPregnancy outcomesAdverse outcomesIL-1βTrophoblast responsesExtravillous trophoblastsHigh riskPreeclampsiaDanger signalsBacterial infectionsVEGF secretionInflammationAntiphospholipid Antibodies Inhibit Trophoblast Toll‐Like Receptor and Inflammasome Negative Regulators
Mulla MJ, Weel IC, Potter JA, Gysler SM, Salmon JE, Peraçoli MTS, Rothlin CV, Chamley LW, Abrahams VM. Antiphospholipid Antibodies Inhibit Trophoblast Toll‐Like Receptor and Inflammasome Negative Regulators. Arthritis & Rheumatology 2018, 70: 891-902. PMID: 29342502, PMCID: PMC5984662, DOI: 10.1002/art.40416.Peer-Reviewed Original ResearchConceptsGrowth arrest-specific protein 6Quantitative reverse transcription polymerase chain reactionEnzyme-linked immunosorbent assayLigand growth arrest-specific protein 6TAM receptor functionTrophoblast inflammationAntiphospholipid antibodiesInflammasome functionReceptor functionToll-like receptor 4Human first-trimester trophoblastsTAM receptor signalingGlycoprotein I antibodiesInterleukin-8 responseRobust inflammatory responseToll-like receptorsEffects of aPLReverse transcription-polymerase chain reactionIL-1β responseIL-1β secretionFirst trimester trophoblastsTranscription-polymerase chain reactionAutophagy inducer rapamycinPlacental inflammationSubsequent TLR
2017
Viral Infection Sensitizes Human Fetal Membranes to Bacterial Lipopolysaccharide by MERTK Inhibition and Inflammasome Activation.
Cross SN, Potter JA, Aldo P, Kwon JY, Pitruzzello M, Tong M, Guller S, Rothlin CV, Mor G, Abrahams VM. Viral Infection Sensitizes Human Fetal Membranes to Bacterial Lipopolysaccharide by MERTK Inhibition and Inflammasome Activation. The Journal Of Immunology 2017, 199: 2885-2895. PMID: 28916522, PMCID: PMC5659726, DOI: 10.4049/jimmunol.1700870.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedChorioamnionitisC-Mer Tyrosine KinaseExtraembryonic MembranesFemaleGammaherpesvirinaeHerpesviridae InfectionsHerpesvirus 2, HumanHumansImmunizationInflammasomesIntercellular Signaling Peptides and ProteinsInterleukin-1betaLipopolysaccharidesMiceMice, Inbred C57BLMice, KnockoutPregnancyPremature BirthProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesConceptsFetal membranesViral infectionImmune responseTAM receptorsSubsequent preterm birthAdverse pregnancy outcomesIL-1β productionIL-1β responseHerpes viral infectionsInnate immune responseVivo mouse modelHuman fetal membranesAggravated inflammationIL-1β processingPregnancy outcomesPreterm birthAssociated complicationsPremature rupturePregnant womenLocal infectionInflammasome activationMerTK inhibitionMouse modelBacterial LPSLigand expressionMechanisms of Antiphospholipid Antibody-Mediated Pregnancy Morbidity
Salmon J, Mineo C, Giles I, Chamley L, Meroni P, Abrahams V. Mechanisms of Antiphospholipid Antibody-Mediated Pregnancy Morbidity. 2017, 117-143. DOI: 10.1007/978-3-319-55442-6_6.Peer-Reviewed Original ResearchIntrauterine growth restrictionPregnancy complicationsAntiphospholipid syndromeAntiphospholipid antibodiesRecurrent early pregnancy lossImpaired placental functionLate obstetrical complicationsNon-thrombotic eventsPartial beneficial effectEarly pregnancy lossMaternal-fetal interfacePregnancy morbidityAPS patientsObstetrical complicationsThrombotic eventsTrophoblast functionsPregnancy lossGrowth restrictionPlacental functionHigh riskComplicationsPathogenic mechanismsComplement activationBeneficial effectsPatients
2016
Antiphospholipid antibody-induced miR-146a-3p drives trophoblast interleukin-8 secretion through activation of Toll-like receptor 8
Gysler SM, Mulla MJ, Guerra M, Brosens JJ, Salmon JE, Chamley LW, Abrahams VM. Antiphospholipid antibody-induced miR-146a-3p drives trophoblast interleukin-8 secretion through activation of Toll-like receptor 8. Molecular Human Reproduction 2016, 22: 465-474. PMID: 27029214, PMCID: PMC4941806, DOI: 10.1093/molehr/gaw027.Peer-Reviewed Original ResearchConceptsToll-like receptor 4IL-8 secretionAdverse pregnancy outcomesTrophoblast-derived exosomesHealthy pregnant controlsMiR-146aTrophoblast cellsMiR-155MiR-210Pregnancy complicationsAntiphospholipid syndromePregnant controlsTLR4 antagonistHTR8 cellsHuman first-trimester extravillous trophoblast cell lineFirst trimester extravillous trophoblast cell lineRelated adverse pregnancy outcomesAbsence of aPLMiR expression levelsPanel of miRsObstetric antiphospholipid syndromeExtravillous trophoblast cell lineToll-like receptor 8Pro-inflammatory effectsAmerican Heart Association
2014
Single- and double-stranded viral RNA generate distinct cytokine and antiviral responses in human fetal membranes
Bakaysa SL, Potter JA, Hoang M, Han CS, Guller S, Norwitz ER, Abrahams VM. Single- and double-stranded viral RNA generate distinct cytokine and antiviral responses in human fetal membranes. Molecular Human Reproduction 2014, 20: 701-708. PMID: 24723465, PMCID: PMC4072183, DOI: 10.1093/molehr/gau028.Peer-Reviewed Original ResearchConceptsHuman fetal membranesToll-like receptorsMIP-1βMIP-1αFetal membranesAntiviral responseIL-1βIL-6IL-2Viral infectionG-CSFCytokine/chemokine profilesViral ssRNAAdverse pregnancy outcomesMaternal-fetal interfaceInfection-associated inflammationMCP-1 secretionViral dsRNA analogueTNF-α productionMIP-1α secretionTLR adapter proteinsExpression of IFNβPregnancy outcomesCytokine profileChemokine profilesHuman Fetal Membranes Generate Distinct Cytokine Profiles in Response to Bacterial Toll-Like Receptor and Nod-Like Receptor Agonists1
Hoang M, Potter JA, Gysler SM, Han CS, Guller S, Norwitz ER, Abrahams VM. Human Fetal Membranes Generate Distinct Cytokine Profiles in Response to Bacterial Toll-Like Receptor and Nod-Like Receptor Agonists1. Biology Of Reproduction 2014, 90: 39, 1-9. PMID: 24429216, PMCID: PMC4076407, DOI: 10.1095/biolreprod.113.115428.Peer-Reviewed Original ResearchConceptsBacterial toll-like receptorsToll-like receptorsPathogen-associated molecular patternsInnate immune pattern recognition receptorsNOD-like receptorsPattern recognition receptorsImmune pattern recognition receptorsCytokine profileIL1B secretionFetal membranesCpG ODNCaspase-1Subsequent preterm birthInflammatory cytokine profilePreterm premature ruptureDistinct cytokine profilesMaternal-fetal interfaceInfection-associated inflammationMild stimulatory effectNLR agonistsPreterm birthPremature ruptureProinflammatory cytokinesCytokine productionMCP-1Interferon-alpha and angiogenic dysregulation in pregnant lupus patients destined for preeclampsia
Andrade D, Kim M, Blanco L, Karumanchi S, Koo G, Redecha P, Kirou K, Alvarez A, Mulla M, Crow M, Abrahams V, Kaplan M, Salmon J. Interferon-alpha and angiogenic dysregulation in pregnant lupus patients destined for preeclampsia. Arthritis Research & Therapy 2014, 16: a28. PMCID: PMC4179538, DOI: 10.1186/ar4644.Peer-Reviewed Original Research
2013
A Role for Uric Acid and the Nalp3 Inflammasome in Antiphospholipid Antibody-Induced IL-1β Production by Human First Trimester Trophoblast
Mulla MJ, Salmon JE, Chamley LW, Brosens JJ, Boeras CM, Kavathas PB, Abrahams VM. A Role for Uric Acid and the Nalp3 Inflammasome in Antiphospholipid Antibody-Induced IL-1β Production by Human First Trimester Trophoblast. PLOS ONE 2013, 8: e65237. PMID: 23762324, PMCID: PMC3675211, DOI: 10.1371/journal.pone.0065237.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, AntiphospholipidAntiphospholipid SyndromeBeta 2-Glycoprotein ICARD Signaling Adaptor ProteinsCarrier ProteinsCaspase 1Cell LineCytoskeletal ProteinsFemaleGene Expression RegulationHumansInflammasomesInterleukin-1betaMiceNLR Family, Pyrin Domain-Containing 3 ProteinPregnancyPregnancy Trimester, FirstProtein PrecursorsSignal TransductionToll-Like Receptor 4TrophoblastsUric AcidConceptsIL-1β productionIntrauterine growth restrictionIL-1β secretionAntiphospholipid syndromeIL-1β processingAntiphospholipid antibodiesIL-1βHuman first trimester trophoblast cell lineFirst trimester trophoblast cell lineUric acidNalp3/ASC inflammasomeHuman first trimester trophoblast cellsToll-like receptor 4Human first-trimester trophoblastsFirst trimester trophoblast cellsAnti-β2GPI AbsAdverse pregnancy outcomesAnti-β2GPI antibodiesRecurrent pregnancy lossTLR4-dependent mannerApoptosis-associated speck-like proteinMaternal-fetal interfaceFirst trimester trophoblastsSpeck-like proteinTrophoblast cell line