2020
Trophoblast-secreted soluble-PD-L1 modulates macrophage polarization and function
Zhang Y, Aldo P, You Y, Ding J, Kaislasuo J, Petersen JF, Lokkegaard E, Peng G, Paidas MJ, Simpson S, Pal L, Guller S, Liu H, Liao AH, Mor G. Trophoblast-secreted soluble-PD-L1 modulates macrophage polarization and function. Journal Of Leukocyte Biology 2020, 108: 983-998. PMID: 32386458, PMCID: PMC8190653, DOI: 10.1002/jlb.1a0420-012rr.Peer-Reviewed Original ResearchConceptsSoluble PD-L1Macrophage polarizationTrophoblast cellsCell death ligand 1PD-L1/PDPD-1 blockageDeath ligand 1Macrophage differentiationModulates macrophage polarizationExpression/secretionDecidual macrophagesHealthy pregnancyPD-L1Pregnant womenTLR4 ligationM2 phenotypeExpression of typeFetal developmentLPS activationMacrophagesIFNPlacenta developmentLigand 1Constitutive productionGestation
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 expression
2014
Toll‐like Receptor‐Mediated Responses by Placental Hofbauer Cells (HBCs): A Potential Pro‐Inflammatory Role for Fetal M2 Macrophages
Young OM, Tang Z, Niven‐Fairchild T, Tadesse S, Krikun G, Norwitz ER, Mor G, Abrahams VM, Guller S. Toll‐like Receptor‐Mediated Responses by Placental Hofbauer Cells (HBCs): A Potential Pro‐Inflammatory Role for Fetal M2 Macrophages. American Journal Of Reproductive Immunology 2014, 73: 22-35. PMID: 25345551, PMCID: PMC4268350, DOI: 10.1111/aji.12336.Peer-Reviewed Original ResearchConceptsHofbauer cellsHuman umbilical vein endothelial cellsM2 macrophagesTLR-3TLR-4Potential pro-inflammatory roleToll-like receptor functionPlacental villous coreAdverse pregnancy outcomesPro-inflammatory rolePlacental Hofbauer cellsIL-6 secretionToll-like receptorsPolycytidylic acid treatmentUmbilical vein endothelial cellsFetal inflammationPregnancy outcomesVein endothelial cellsTLR agonistsTLR-2Cytokine secretionInflammatory responseVillous corePlacental fibroblastsReceptor functionTrophoblast Induces Monocyte Differentiation Into CD14+/CD16+ Macrophages
Aldo PB, Racicot K, Craviero V, Guller S, Romero R, Mor G. Trophoblast Induces Monocyte Differentiation Into CD14+/CD16+ Macrophages. American Journal Of Reproductive Immunology 2014, 72: 270-284. PMID: 24995492, PMCID: PMC4230492, DOI: 10.1111/aji.12288.Peer-Reviewed Original ResearchConceptsUnique macrophage phenotypeMacrophage phenotypeMonocyte differentiationFirst trimester trophoblast cellsPeripheral blood monocytesPhenotype of macrophagesCD14 surface expressionNormal deciduaHealthy pregnancyIL-10Chemokine productionEarly pregnancyIP-10Monocyte exposureIL-1BBlood monocytesDecidual phenotypePhagocytic capacityTrophoblast cellsFlow cytometryMorphologic changesMacrophagesMonocytesSurface expressionPlacenta developmentHuman 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-1
2012
Lipopolysaccharide Appears to Activate Human Endometrial Endothelial Cells Through TLR‐4‐Dependent and TLR‐4‐Independent Mechanisms
Krikun G, Trezza J, Shaw J, Rahman M, Guller S, Abrahams VM, Lockwood CJ. Lipopolysaccharide Appears to Activate Human Endometrial Endothelial Cells Through TLR‐4‐Dependent and TLR‐4‐Independent Mechanisms. American Journal Of Reproductive Immunology 2012, 68: 233-237. PMID: 22672000, PMCID: PMC3418410, DOI: 10.1111/j.1600-0897.2012.01164.x.Peer-Reviewed Original ResearchConceptsEndometrial endothelial cellsTissue factor expressionHuman endometrial endothelial cellsToll-like receptorsLPS-RSFactor expressionEndothelial cellsBacterial lipopolysaccharideTLR-4Innate immunityCytokine/chemokine responsesTLR-4 antagonistGram-negative bacterial lipopolysaccharideChemokine responsesIL-6IL-8Cytokine secretionG-CSFWestern blotLipopolysaccharideBacterial componentsCell-free supernatantMD-2ImmunitySecretion
2010
Focal Increases of Fetal Macrophages in Placentas from Pregnancies with Histological Chorioamnionitis: Potential Role of Fibroblast Monocyte Chemotactic Protein‐1
Toti P, Arcuri F, Tang Z, Schatz F, Zambrano E, Mor G, Niven‐Fairchild T, Abrahams VM, Krikun G, Lockwood CJ, Guller S. Focal Increases of Fetal Macrophages in Placentas from Pregnancies with Histological Chorioamnionitis: Potential Role of Fibroblast Monocyte Chemotactic Protein‐1. American Journal Of Reproductive Immunology 2010, 65: 470-479. PMID: 21087336, PMCID: PMC3071455, DOI: 10.1111/j.1600-0897.2010.00927.x.Peer-Reviewed Original ResearchConceptsHistopathological chorioamnionitisMCP-1 mRNAFocal increaseMonocyte chemotactic protein-1Subset of pregnanciesAdverse neonatal outcomesProtein expressionPro-inflammatory cytokinesMaternal-fetal interfaceChemotactic protein-1MCP-1 expressionTerm placental villiHistological chorioamnionitisNeonatal outcomesCytokine cascadeIL-1βInflammatory cytokinesQuantitative real-time PCRFetal monocytesReal-time PCRHuman term placental villiPlacental villiControl groupBacterial productsTreatment of fibroblasts
2009
ORIGINAL ARTICLE: Regulation of Nod1 and Nod2 in First Trimester Trophoblast Cells
Mulla MJ, Yu AG, Cardenas I, Guller S, Panda B, Abrahams VM. ORIGINAL ARTICLE: Regulation of Nod1 and Nod2 in First Trimester Trophoblast Cells. American Journal Of Reproductive Immunology 2009, 61: 294-302. PMID: 19260860, DOI: 10.1111/j.1600-0897.2009.00694.x.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisBenzamidesCells, CulturedCytokinesDiaminopimelic AcidFemaleGene Expression Regulation, DevelopmentalHumansLipopolysaccharidesNF-kappa BNod1 Signaling Adaptor ProteinNod2 Signaling Adaptor ProteinPregnancyPregnancy Trimester, FirstSequence DeletionSignal TransductionThiazolesToll-Like Receptor 4TransgenesTrophoblastsConceptsFirst trimester trophoblast cellsTrophoblast cellsExpression of NOD1Cytoplasmic pattern recognition receptorsProduction of cytokinesNOD2 mRNA expressionPattern recognition receptorsNOD2 expressionCytokine responsesInflammatory responseNOD2 activationNOD1 activationNFkappaB inhibitorRecognition receptorsNOD1Nod1 stimulationNOD2Bacterial lipopolysaccharideMRNA expressionTLR4LipopolysaccharideNFkappaB pathwayRT-PCRBacterial peptidesTrophoblast
2007
Expression of Toll-like receptors in the human decidua.
Krikun G, Lockwood CJ, Abrahams VM, Mor G, Paidas M, Guller S. Expression of Toll-like receptors in the human decidua. Histology And Histopathology 2007, 22: 847-54. PMID: 17503341, DOI: 10.14670/hh-22.847.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Vesicular TransportCells, CulturedDeciduaEndometriumEndothelial CellsFemaleHumansImmunity, InnateImmunohistochemistryInterleukinsLipopolysaccharidesMyeloid Differentiation Factor 88NF-kappa BPeptidoglycanPoly I-CPregnancyPregnancy Trimester, FirstPregnancy Trimester, ThirdReverse Transcriptase Polymerase Chain ReactionRNA, MessengerSignal TransductionToll-Like ReceptorsConceptsToll-like receptorsHuman deciduaFirst trimester elective terminationMaternal spiral arteriesInnate immune responseCesarean sectionSpiral arteriesThird trimesterCytokine productionElective terminationDecidual tissuesImmune responseLate gestationPregnant endometriumFetal membranesSurveillance moleculeHost defensePregnancyDeciduaMRNA levelsReceptorsMicrobial pathogensTrimesterEndometriumArteryCell Type-specific Expression and Function of Toll-like Receptors 2 and 4 in Human Placenta: Implications in Fetal Infection
Ma Y, Krikun G, Abrahams VM, Mor G, Guller S. Cell Type-specific Expression and Function of Toll-like Receptors 2 and 4 in Human Placenta: Implications in Fetal Infection. Placenta 2007, 28: 1024-1031. PMID: 17588655, PMCID: PMC2064901, DOI: 10.1016/j.placenta.2007.05.003.Peer-Reviewed Original ResearchConceptsInnate immune responseIL-8 levelsToll-like receptorsTLR-4Immune responseTLR-2TLR functionTerm placentaToll-like receptor 2Endothelial cellsAdverse fetal outcomesTLR-2 expressionMaternal-fetal interfacePathogen-associated molecular patternsHuman term placentaCell type-specific expressionGram-negative bacterial lipopolysaccharideFetal outcomesPlacental infectionTLR expressionFetal infectionLPS treatmentMajor cell typesImmunohistochemical analysisStem villi
2005
Alterations in Syncytiotrophoblast Cytokine Expression Following Treatment with Lipopolysaccharide
Ma Y, Mor G, Abrahams VM, Buhimschi IA, Buhimschi CS, Guller S. Alterations in Syncytiotrophoblast Cytokine Expression Following Treatment with Lipopolysaccharide. American Journal Of Reproductive Immunology 2005, 55: 12-18. PMID: 16364007, DOI: 10.1111/j.1600-0897.2005.00347.x.Peer-Reviewed Original ResearchConceptsCytokine expressionLPS treatmentInflammatory compoundsAnti-inflammatory cytokinesIL-8 levelsInterleukin-8 levelsAnti-inflammatory compoundsEnzyme-linked immunosorbent assayCell typesCytokine levelsGlucocorticoid treatmentMaternal bloodDEX treatmentPlacental syncytiumSyncytiotrophoblastImmunosorbent assayLPSPrimary culturesTreatmentCytokinesFourfold increaseExpressionSyncytiaGestationLevelsThrombin-dependent regulation of matrix metalloproteinase (MMP)-9 levels in human fetal membranes*
Stephenson CD, Lockwood CJ, Ma Y, Guller S. Thrombin-dependent regulation of matrix metalloproteinase (MMP)-9 levels in human fetal membranes*. The Journal Of Maternal-Fetal & Neonatal Medicine 2005, 18: 17-22. PMID: 16105787, DOI: 10.1080/14767050500123632.Peer-Reviewed Original ResearchConceptsMMP-9 levelsMMP-9MMP-1Matrix metalloproteinaseAmniochorionic membranesThrombin receptor agonist peptidePreterm premature ruptureAnti-inflammatory steroidsMajor risk factorMMP-9 expressionThrombin treatmentThrombin receptor agonistPresence of lipopolysaccharideHuman fetal membranesPremature ruptureReceptor agonistRisk factorsSuch hemorrhageDEX treatmentMMP levelsTIMP-1Thrombin receptorTissue inhibitorAgonist peptideFetal membranes
2004
Differential Effects of Lipopolysaccharide and Thrombin on Interleukin‐8 Expression in Syncytiotrophoblasts and Endothelial Cells: Implications for Fetal Survival
MA Y, KADNER SS, GULLER S. Differential Effects of Lipopolysaccharide and Thrombin on Interleukin‐8 Expression in Syncytiotrophoblasts and Endothelial Cells: Implications for Fetal Survival. Annals Of The New York Academy Of Sciences 2004, 1034: 236-244. PMID: 15731315, DOI: 10.1196/annals.1335.025.Peer-Reviewed Original ResearchConceptsCytokine expressionEndothelial cellsFetal survivalInfection-associated changesPlacental cytokine expressionTissue factor-initiated blood coagulationIL-8 levelsInterleukin-8 levelsAnti-inflammatory steroidsMaintenance of pregnancyIL-8 expressionIL-8 mRNAInterleukin-8 expressionEffect of thrombinHuman umbilical vein endothelial cellsHuman term placentaUmbilical vein endothelial cellsVein endothelial cellsCytokine responsesCytokine productionProinflammatory processesIL-8Inflammatory responseLPS treatmentIntervillous space