2023
Leptin-Mediated Induction of IL-6 Expression in Hofbauer Cells Contributes to Preeclampsia Pathogenesis
Ozmen A, Nwabuobi C, Tang Z, Guo X, Larsen K, Guller S, Blas J, Moore M, Kayisli U, Lockwood C, Guzeloglu-Kayisli O. Leptin-Mediated Induction of IL-6 Expression in Hofbauer Cells Contributes to Preeclampsia Pathogenesis. International Journal Of Molecular Sciences 2023, 25: 135. PMID: 38203306, PMCID: PMC10778808, DOI: 10.3390/ijms25010135.Peer-Reviewed Original ResearchConceptsIL-6 expressionHofbauer cellsP65 NF-κBIL-6NF-κBLeptin levelsPreeclampsia pathogenesisElevated serum interleukin-6 levelsSerum interleukin-6 levelsERK1/2 MAPKInterleukin-6 levelsPro-inflammatory phenotypeAnti-inflammatory phenotypeLeptin receptor expressionIL-6 productionPathogenesis of PEPlacental leptin productionPhosphorylation levelsERK1/2 MAPK inhibitorIL-6 regulationConcentration-dependent mannerPE patientsHuman pregnancySecond trimesterLeptin concentrations
2022
Insulin increases placental triglyceride as a potential mechanism for fetal adiposity in maternal obesity
Anam AK, Cooke KM, Dratver MB, O'Bryan JV, Perley LE, Guller SM, Hwang JJ, Taylor HS, Goedeke L, Kliman HJ, Vatner DF, Flannery CA. Insulin increases placental triglyceride as a potential mechanism for fetal adiposity in maternal obesity. Molecular Metabolism 2022, 64: 101574. PMID: 35970449, PMCID: PMC9440306, DOI: 10.1016/j.molmet.2022.101574.Peer-Reviewed Original ResearchConceptsDe novo lipogenesisFetal adiposityFatty acid uptakeMaternal obesityObese womenNormal weightExcess adiposityVillous explantsInsulin receptorNewborns of mothersNormal-weight womenAcid uptakePlacental villous explantsTranscription factor SREBP-1Insulin-like growth factor 2Effect of insulinFatty acid oxidationPlacental triglyceridesPlacental responsesElevated triglyceridesMaternal hyperglycemiaWeight womenGrowth factor 2Diabetes riskPlacental metabolism
2021
Maternal respiratory SARS-CoV-2 infection in pregnancy is associated with a robust inflammatory response at the maternal-fetal interface
Lu-Culligan A, Chavan AR, Vijayakumar P, Irshaid L, Courchaine EM, Milano KM, Tang Z, Pope SD, Song E, Vogels CBF, Lu-Culligan WJ, Campbell KH, Casanovas-Massana A, Bermejo S, Toothaker JM, Lee HJ, Liu F, Schulz W, Fournier J, Muenker MC, Moore AJ, Team Y, Konnikova L, Neugebauer KM, Ring A, Grubaugh ND, Ko AI, Morotti R, Guller S, Kliman HJ, Iwasaki A, Farhadian SF. Maternal respiratory SARS-CoV-2 infection in pregnancy is associated with a robust inflammatory response at the maternal-fetal interface. Med 2021, 2: 591-610.e10. PMID: 33969332, PMCID: PMC8084634, DOI: 10.1016/j.medj.2021.04.016.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 infectionMaternal-fetal interfaceACE2 expressionNatural killerPregnant womenPlacental cellsAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionSARS-CoV-2-infected womenTerm placentaSyndrome coronavirus 2 infectionCoronavirus 2 infectionPotential immune mechanismsRobust inflammatory responseRobust immune responseCoronavirus disease 2019Detectable viral RNAInterferon-related genesLower ACE2 expressionMajority of placentasPregnancy complicationsPlacental histologyHofbauer cellsEarly pregnancyImmune activation
2020
NLRP3 inflammasome function and pyroptotic cell death in human placental Hofbauer cells
Abrahams VM, Tang Z, Mor G, Guller S. NLRP3 inflammasome function and pyroptotic cell death in human placental Hofbauer cells. Journal Of Reproductive Immunology 2020, 142: 103214. PMID: 33152658, PMCID: PMC7770077, DOI: 10.1016/j.jri.2020.103214.Peer-Reviewed Original ResearchConceptsHofbauer cellsCaspase-1 activationIL-1β processingIL-1βInflammasome activationFetal inflammatory response syndromeSubsequent pregnancy complicationsInflammatory response syndromeCell deathNLRP3 inflammasome activationInterleukin-1 betaIL-1β secretionInhibition of P2X7Human term placentaGasdermin D cleavageNLRP3 knockdownPlacental inflammationPyroptotic cell deathFetal inflammationHistologic chorioamnionitisPregnancy complicationsResponse syndromeNLRP3 inflammasomeProtein/gene expressionInflammatory formHerpesvirus-infected Hofbauer cells activate endothelial cells through an IL-1β-dependent mechanism
Hendrix P, Tang Z, Silasi M, Racicot KE, Mor G, Abrahams VM, Guller S. Herpesvirus-infected Hofbauer cells activate endothelial cells through an IL-1β-dependent mechanism. Placenta 2020, 91: 59-65. PMID: 32174308, PMCID: PMC7078070, DOI: 10.1016/j.placenta.2020.01.010.Peer-Reviewed Original ResearchConceptsHuman umbilical vein endothelial cellsHofbauer cellsIL-1βAdhesion molecule-1Placental viral infectionsIL-8Viral infectionFetal inflammationEndothelial cellsE-selectinMolecule-1IL-1 receptor antagonistVascular adhesion molecule-1Intercellular adhesion molecule-1Adverse pregnancy outcomesMHV-68 infectionIL-1β secretionICAM-1 mRNAUmbilical vein endothelial cellsUmbilical endothelial cellsPregnancy outcomesVein endothelial cellsIL-1raPlacental macrophagesHUVEC expression
2017
Dynamics of Base Excision Repair at the Maternal–Fetal Interface in Pregnancies Complicated by Preeclampsia
Tadesse S, Norwitz NG, Guller S, Arcuri F, Toti P, Norwitz ER, Kidane D. Dynamics of Base Excision Repair at the Maternal–Fetal Interface in Pregnancies Complicated by Preeclampsia. Reproductive Sciences 2017, 24: 856-864. PMID: 27707956, DOI: 10.1177/1933719116670519.Peer-Reviewed Original ResearchConceptsMaternal-fetal interfaceOxidative stressNormotensive controlsPlacental tissueHypoxia/reperfusion (H/R) modelPlacental endothelial dysfunctionPlacentas of womenHealthy control subjectsApyrimidinic endonuclease 1PE placental tissuesPregnancy ComplicatedEndothelial dysfunctionPreeclamptic womenPerinatal mortalityReperfusion modelControl subjectsDecidual cellsPathological basisVivo comparative studyPreeclampsiaMaternal cellsFetal cellsAPE1 expressionSignificant increaseWomen
2016
Zika virus infection of Hofbauer cells
Simoni MK, Jurado KA, Abrahams VM, Fikrig E, Guller S. Zika virus infection of Hofbauer cells. American Journal Of Reproductive Immunology 2016, 77 PMID: 27966815, PMCID: PMC5299062, DOI: 10.1111/aji.12613.Peer-Reviewed Original ResearchConceptsCongenital Zika syndromeHofbauer cellsZika virusZIKV infectionDevelopment of CZSDengue virusSpread of ZIKVVertical transmissionFetal placental macrophagesPlacental Hofbauer cellsZika virus infectionAntenatal infectionNeonatal outcomesPlacental responsesZika syndromeVirus infectionCurrent evidenceCongenital abnormalitiesRecent studiesNeonatal developmentFetal capillariesRelated flavivirusesInfectionSpecific molecular mechanismsCertain virusesH19 long noncoding RNA alters trophoblast cell migration and invasion by regulating TβR3 in placentae with fetal growth restriction
Zuckerwise L, Li J, Lu L, Men Y, Geng T, Buhimschi CS, Buhimschi IA, Bukowski R, Guller S, Paidas M, Huang Y. H19 long noncoding RNA alters trophoblast cell migration and invasion by regulating TβR3 in placentae with fetal growth restriction. Oncotarget 2016, 7: 38398-38407. PMID: 27223264, PMCID: PMC5122399, DOI: 10.18632/oncotarget.9534.Peer-Reviewed Original ResearchConceptsFetal growth restrictionGrowth restrictionExtravillous trophoblastsDownregulation of H19Type III TGF-β receptorCell migrationEVT cell migrationNon-canonical TGFTGF-β receptorFGR placentasNeurodevelopmental impairmentPerinatal mortalityRisk factorsTherapeutic modalitiesEVT cellsH19 knockdownOnset disordersPlacentaInvasionMolecular mechanismsH19Let-7Novel regulatory targetMorbidityRegulatory pathwaysInflammatory processes are specifically enhanced in endothelial cells by placental-derived TNF-α: Implications in preeclampsia (PE)
Shaw J, Tang Z, Schneider H, Saljé K, Hansson SR, Guller S. Inflammatory processes are specifically enhanced in endothelial cells by placental-derived TNF-α: Implications in preeclampsia (PE). Placenta 2016, 43: 1-8. PMID: 27324092, DOI: 10.1016/j.placenta.2016.04.015.Peer-Reviewed Original ResearchConceptsPro-inflammatory cytokine secretionMaternal perfusateCytokine secretionEndothelial dysfunctionActivation markersEndothelial cellsTNF-α blocking antibodyDual perfusion modelMaternal endothelial dysfunctionPro-inflammatory cytokinesMCP-1 secretionTNF-α actionEndothelial cell linePlacental pathophysiologyEndothelial activationIL-6IL-8Maternal endotheliumInflammatory processDual perfusionMaternal circulationBlocking antibodiesPreeclampsiaTNFPerfusion model
2013
Decreased Levels of Folate Receptor‐β and Reduced Numbers of Fetal Macrophages (Hofbauer Cells) in Placentas from Pregnancies with Severe Pre‐Eclampsia
Tang Z, Buhimschi IA, Buhimschi CS, Tadesse S, Norwitz E, Niven‐Fairchild T, Huang S, Guller S. Decreased Levels of Folate Receptor‐β and Reduced Numbers of Fetal Macrophages (Hofbauer Cells) in Placentas from Pregnancies with Severe Pre‐Eclampsia. American Journal Of Reproductive Immunology 2013, 70: 104-115. PMID: 23480364, PMCID: PMC3686834, DOI: 10.1111/aji.12112.Peer-Reviewed Original ResearchConceptsSpontaneous preterm birthPre-eclampsiaAge-matched normotensive controlsPreterm pre-eclampsiaSevere pre eclampsiaPathophysiology of PEPregnancy complicationsPreterm birthNormotensive controlsHofbauer cellsFetal mortalityUnknown etiologyPlacental expressionSPTB groupMacrophage functionPlacentaSevere preFetal macrophagesWestern blottingMajor causeProtein expressionPlacental genesReverse transcription-PCR analysisMarker mRNAsTranscription-PCR analysis
2012
Glucocorticoids Enhance CD163 Expression in Placental Hofbauer Cells
Tang Z, Niven-Fairchild T, Tadesse S, Norwitz ER, Buhimschi CS, Buhimschi IA, Guller S. Glucocorticoids Enhance CD163 Expression in Placental Hofbauer Cells. Endocrinology 2012, 154: 471-482. PMID: 23142809, PMCID: PMC3529384, DOI: 10.1210/en.2012-1575.Peer-Reviewed Original ResearchConceptsHofbauer cellsGC treatmentGC administrationCD163 expressionDEX treatmentCD68 mRNASpontaneous preterm birthMacrophage marker genesPlacental explant culturesAntiinflammatory M2 macrophagesHuman term placentaExpression of FRPreterm deliveryPreterm birthCD163 mRNAM2 macrophagesReceptor mRNAGC actionSynthetic GCFetal capillariesTerm placentaPlacental fibroblastsFlow cytometryCD163 proteinFetal macrophages
2011
Isolation of Hofbauer Cells from Human Term Placentas with High Yield and Purity
Tang Z, Tadesse S, Norwitz E, Mor G, Abrahams VM, Guller S. Isolation of Hofbauer Cells from Human Term Placentas with High Yield and Purity. American Journal Of Reproductive Immunology 2011, 66: 336-348. PMID: 21545365, PMCID: PMC3154981, DOI: 10.1111/j.1600-0897.2011.01006.x.Peer-Reviewed Original ResearchConceptsHofbauer cellsHuman term placentaTerm placentaComplications of pregnancyCell typesMacrophage functionPhagocytotic activityFlow cytometryVillus functionConsensus methodologyVacuolated appearancePhagocytosis assaysPlacentaPercoll gradientCTFuture studiesFibroblastsHBCCellsDaysHigh levelsComplicationsCulture mediumPregnancyMacrophagesPlacental Hofbauer cells and complications of pregnancy
Tang Z, Abrahams VM, Mor G, Guller S. Placental Hofbauer cells and complications of pregnancy. Annals Of The New York Academy Of Sciences 2011, 1221: 103-108. PMID: 21401637, PMCID: PMC3707113, DOI: 10.1111/j.1749-6632.2010.05932.x.Peer-Reviewed Original ResearchConceptsComplications of pregnancyHofbauer cellsHistological chorioamnionitisCytokine-mediated inflammationPlacental Hofbauer cellsPlacental pathophysiologyPlacental macrophagesUnknown etiologyPlacental functionMajor cell typesVillus functionComplicationsPregnancyCell typesSpecific roleGene expressionChorioamnionitisVillitisCellsInflammationGestationPathophysiologyEtiologyPlacentaMacrophages
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 fibroblastsProtein composition of microparticles shed from human placenta during placental perfusion: Potential role in angiogenesis and fibrinolysis in preeclampsia
Guller S, Tang Z, Ma YY, Di Santo S, Sager R, Schneider H. Protein composition of microparticles shed from human placenta during placental perfusion: Potential role in angiogenesis and fibrinolysis in preeclampsia. Placenta 2010, 32: 63-69. PMID: 21074265, PMCID: PMC3762591, DOI: 10.1016/j.placenta.2010.10.011.Peer-Reviewed Original ResearchConceptsPlasminogen activator inhibitorMaternal perfusateSFlt-1Maternal endothelial cell dysfunctionFms-like tyrosine kinasePathophysiology of preeclampsiaMaternal-fetal interfaceEndothelial cell dysfunctionAnti-angiogenic actionFollowing relative levelsPlacental damagePlacental perfusionMaternal serumNormal pregnancyPlacental pathophysiologyAnnexin V bindingSyncytiotrophoblast microparticlesDual perfusionAngiogenic balanceCell dysfunctionMaternal bloodPreeclampsiaActivator inhibitorCytometric analysisLevel of expressionRole of GnRH–GnRH receptor signaling at the maternal-fetal interface
Lee HJ, Snegovskikh VV, Park JS, Foyouzi N, Han KT, Hodgson EJ, Guller S, Norwitz ER. Role of GnRH–GnRH receptor signaling at the maternal-fetal interface. Fertility And Sterility 2010, 94: 2680-2687. PMID: 20400076, DOI: 10.1016/j.fertnstert.2010.03.016.Peer-Reviewed Original ResearchConceptsGnRHR-I mRNAMaternal-fetal interfaceDecidual stromal cellsHCG productionGnRH-IISelect cytokinesTrophoblast cellsCell linesEffects of GnRHUniversity Teaching HospitalExpression of GnRHFunction of GnRHReverse transcription-polymerase chain reactionDose-dependent fashionHuman trophoblast cellsTerm deliveryPolymerase chain reactionTeaching hospitalGnRH receptorMAIN OUTCOMEGnRHHuman trophoblastsStromal cellsWestern blotImmortalized cell lines
2009
Role of the syncytium in placenta-mediated complications of preeclampsia
Guller S. Role of the syncytium in placenta-mediated complications of preeclampsia. Thrombosis Research 2009, 124: 389-392. PMID: 19535132, PMCID: PMC2764997, DOI: 10.1016/j.thromres.2009.05.016.Peer-Reviewed Original ResearchConceptsPlasminogen activator inhibitor-1Fms-like tyrosine kinase-1Complications of preeclampsiaIntrauterine growth restrictionPathophysiology of preeclampsiaTyrosine kinase-1Immune cell functionAnti-angiogenic factorsActivator inhibitor-1Potential protective actionMaternal hemostasisSoluble endoglinEndothelial functionReperfusion injuryMaternal endotheliumMaternal mortalityRelease of microparticlesGrowth restrictionMaternal bloodPreeclampsiaSensitive markerMajor causeInhibitor-1Protective actionReactive oxygen species
2008
Placental expression of ceruloplasmin in pregnancies complicated by severe preeclampsia
Guller S, Buhimschi CS, Y Y, Huang T, Yang L, Kuczynski E, Zambrano E, Lockwood CJ, Buhimschi IA. Placental expression of ceruloplasmin in pregnancies complicated by severe preeclampsia. Laboratory Investigation 2008, 88: 1057-1067. PMID: 18679377, PMCID: PMC2682720, DOI: 10.1038/labinvest.2008.74.Peer-Reviewed Original ResearchConceptsPlasminogen activator inhibitor-1Severe preeclampsiaReperfusion injurySFlt-1Soluble fms-like tyrosine kinase-1Fms-like tyrosine kinase-1Ischemia/reperfusion injuryLife-threatening syndromeSubsequent reperfusion injuryTerm control groupPathophysiology of preeclampsiaTyrosine kinase-1Activator inhibitor-1Release of factorsSignificant increasePresence of mRNAUpregulation of mRNACeruloplasmin mRNAPlacental damagePlacental factorsMicroarray gene profilingEndothelium dysfunctionPE placentasQuantitative real-time PCRIntervillous spaceThe Placental Syncytium and the Pathophysiology of Preeclampsia and Intrauterine Growth Restriction
Guller S, Y. Y, Fu H, Krikun G, Abrahams VM, Mor G. The Placental Syncytium and the Pathophysiology of Preeclampsia and Intrauterine Growth Restriction. Annals Of The New York Academy Of Sciences 2008, 1127: 129-133. PMID: 18443340, PMCID: PMC3671376, DOI: 10.1196/annals.1434.015.Peer-Reviewed Original ResearchConceptsIntrauterine growth restrictionPathophysiology of preeclampsiaGrowth restrictionPlacental syncytiumFms-like tyrosine kinase-1Complications of pregnancyPlasminogen activator inhibitor-1Tyrosine kinase-1Activator inhibitor-1Release of factorsPlacental damageSoluble endoglinEndothelium dysfunctionLaser capture microdissectionMaternal bloodAntiangiogenic factorsPreeclampsiaFas ligandWestern blottingInhibitor-1Reactive oxygen speciesCapture microdissectionPregnancyPathophysiologyKinase 1
2007
Cell 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