2023
Cell-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
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
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
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
2012
Nod1, but not the ASC inflammasome, contributes to induction of IL-1β secretion in human trophoblasts after sensing of Chlamydia trachomatis
Kavathas PB, Boeras CM, Mulla MJ, Abrahams VM. Nod1, but not the ASC inflammasome, contributes to induction of IL-1β secretion in human trophoblasts after sensing of Chlamydia trachomatis. Mucosal Immunology 2012, 6: 235-243. PMID: 22763410, PMCID: PMC3465624, DOI: 10.1038/mi.2012.63.Peer-Reviewed Original ResearchMeSH KeywordsCARD Signaling Adaptor ProteinsCarrier ProteinsCell LineChlamydia trachomatisCytoskeletal ProteinsGene ExpressionHumansInflammasomesInterleukin-1betaMyeloid Differentiation Factor 88NLR Family, Pyrin Domain-Containing 3 ProteinNod1 Signaling Adaptor ProteinToll-Like Receptor 2Toll-Like Receptor 4TrophoblastsConceptsIL-1β secretionToll-like receptorsCT infectionIL-1βASC inflammasomeChlamydia trachomatisKey Toll-like receptorsNalp3/ASC inflammasomePro-inflammatory cytokinesIL-1β mRNAIL-1β productionInnate immune pathwaysNOD-like receptorsHuman trophoblast cellsIntracellular bacterial pathogenChlamydia infectionImmune pathwaysObligate intracellular bacterial pathogenTrophoblast cellsHuman trophoblastsCaspase-1InfectionSecretionInflammasomeNOD1
2011
Nod1 Activation by Bacterial iE-DAP Induces Maternal–Fetal Inflammation and Preterm Labor
Cardenas I, Mulla MJ, Myrtolli K, Sfakianaki AK, Norwitz ER, Tadesse S, Guller S, Abrahams VM. Nod1 Activation by Bacterial iE-DAP Induces Maternal–Fetal Inflammation and Preterm Labor. The Journal Of Immunology 2011, 187: 980-986. PMID: 21677137, DOI: 10.4049/jimmunol.1100578.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornCell LineDiaminopimelic AcidDisease Models, AnimalFemaleHumansInfant, NewbornInfant, PrematureInflammationMaternal-Fetal ExchangeMiceMice, Inbred C57BLNod1 Signaling Adaptor ProteinObstetric Labor, PrematurePregnancyPregnancy OutcomeTissue Culture TechniquesTrophoblastsConceptsPattern recognition receptorsPreterm laborCytokine profileNOD1 activationRecognition receptorsInfection-associated preterm laborHuman first-trimester trophoblastsIntracellular pattern recognition receptorsProinflammatory cytokine profileHuman term placental tissueActivation of NOD1Maternal-fetal interfaceInfection-associated inflammationFunction of NOD1Term placental tissueFirst trimester trophoblastsThird trimester trophoblastFetal inflammationPreterm deliveryEmbryonic day 14.5Pregnancy outcomesFetal weightIL-6MCP-1NOD2 stimulation