2025
Estimating the relative rates of lipopolysaccharide synthesis in Escherichia coli K-12 by click chemistry-mediated labeling
Shu S, Mi W. Estimating the relative rates of lipopolysaccharide synthesis in Escherichia coli K-12 by click chemistry-mediated labeling. PLOS ONE 2025, 20: e0325589. PMID: 40549759, PMCID: PMC12184891, DOI: 10.1371/journal.pone.0325589.Peer-Reviewed Original ResearchMeSH KeywordsAzidesClick ChemistryEscherichia coli K12Fluorescent DyesLipopolysaccharidesStaining and LabelingConceptsSynthesized LPSLabelled lipopolysaccharideE. coli K-12 strain MG1655Escherichia coli K-12Investigating bacterial physiologyPhase of bacterial growthLog phase of bacterial growthIn-gel fluorescenceBacterial membrane integritySynthesis rateNon-radioactive approachHost immune interactionsGram-negative bacteriaLipopolysaccharide synthesisLPS synthesisBacterial physiologySynthesis in vivoLPS biogenesisExponential phaseCopper-free click reactionIn-gelLog phaseMembrane integrityBacterial growthFluorescent alkyneEndothelial CLEC5A drives barrier dysfunction and vascular leakage responsible for lung injury in bacterial pneumonia and sepsis
Zhang T, Huang X, Goodwin J, Wen R, Liu Y, Yang Y, Zhang T, Zheng Y, Chen A, Hao P, Tong X, Yang N, Liu C. Endothelial CLEC5A drives barrier dysfunction and vascular leakage responsible for lung injury in bacterial pneumonia and sepsis. Science Advances 2025, 11: eadt7589. PMID: 40498836, PMCID: PMC12154197, DOI: 10.1126/sciadv.adt7589.Peer-Reviewed Original ResearchConceptsVascular leakagePuncture (CLP)-induced polymicrobial sepsisRegulating endothelial barrier functionCLP-challenged miceEndothelial barrier dysfunctionTrans-endothelial electrical resistanceEndothelial barrier functionLipopolysaccharide (LPS)-induced endotoxemiaVascular endothelial cellsPattern recognition receptorsSurvival benefitMultiorgan failurePolymicrobial sepsisTrans-endothelial migrationCecal ligationBacterial pneumoniaLung injuryBarrier dysfunctionVascular injurySingle-cell RNA sequencingDecreased mortalityInflammatory stormBacterial infectionsHeterogeneity of vascular endothelial cellsSepsis
2024
Neuroinflammatory history results in overlapping transcriptional signatures with heroin exposure in the nucleus accumbens and alters responsiveness to heroin in male rats
Floris G, Zanda M, Dabrowski K, Daws S. Neuroinflammatory history results in overlapping transcriptional signatures with heroin exposure in the nucleus accumbens and alters responsiveness to heroin in male rats. Translational Psychiatry 2024, 14: 500. PMID: 39702361, PMCID: PMC11659471, DOI: 10.1038/s41398-024-03203-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBehavior, AnimalHeroinLipopolysaccharidesMaleNeuroinflammatory DiseasesNucleus AccumbensRatsRats, Sprague-DawleyTranscriptomeConceptsResponse to heroinNucleus accumbensHeroin exposureOpioid use disorderSelf-administrationHeroin self-administrationMesolimbic dopamine systemOpioid-induced behaviorsMolecular neuroadaptationsDopamine systemOpioid rewardHeroin intakeBehavioral effectsUse disorderPsychiatric researchLipopolysaccharide (LPS)-induced neuroinflammationPreclinical modelsBehavioral ramificationsSensitivity to opioidsOpioid heroinHeroinMale ratsAccumbensHeightened immune responseNeuroinflammationEzrin drives adaptation of monocytes to the inflamed lung microenvironment
Gudneppanavar R, Di Pietro C, H Öz H, Zhang P, Cheng E, Huang P, Tebaldi T, Biancon G, Halene S, Hoppe A, Kim C, Gonzalez A, Krause D, Egan M, Gupta N, Murray T, Bruscia E. Ezrin drives adaptation of monocytes to the inflamed lung microenvironment. Cell Death & Disease 2024, 15: 864. PMID: 39613751, PMCID: PMC11607083, DOI: 10.1038/s41419-024-07255-8.Peer-Reviewed Original ResearchConceptsActivation of focal adhesion kinaseExtracellular matrixActin-binding proteinsFocal adhesion kinaseLung extracellular matrixKnock-out mouse modelProtein kinase signalingCortical cytoskeletonLoss of ezrinKinase signalingPlasma membraneCell migrationSignaling pathwayEzrinResponse to lipopolysaccharideTissue-resident macrophagesMouse modelLipopolysaccharideCytoskeletonEzrin expressionLung microenvironmentKinaseMonocyte recruitmentProteinAktMaresin-1 Ameliorates Sepsis-Induced Microglial Activation Through Modulation of the P38 MAPK Pathway
Dai M, Sun S, Dai Y, Dou X, Yang J, Chen X, Yang D, Lin Y. Maresin-1 Ameliorates Sepsis-Induced Microglial Activation Through Modulation of the P38 MAPK Pathway. Neurochemical Research 2024, 50: 26. PMID: 39565476, DOI: 10.1007/s11064-024-04280-z.Peer-Reviewed Original ResearchConceptsSepsis-induced neuroinflammationM1-type microgliaPro-inflammatory markersPhosphorylation of p38 MAPKP38 MAPK pathwayP38 MAPKDysregulated immune response to infectionMouse cecum ligationImmune response to infectionExpression of pro-inflammatory markersInhibited phosphorylation of p38 MAPKInduce neuronal degenerationMAPK pathwayPuncture (CLP)-induced sepsis modelPotential therapeutic roleP38 MAPK inhibitor SB203580Combination of SB203580Response to infectionMicroglial cell markersLife-threatening diseaseMAPK inhibitor SB203580Co-administrationCell markersCLP modelCecum ligationGastrodenol suppresses NLRP3/GSDMD mediated pyroptosis and ameliorates inflammatory diseases
Chen P, Wang Y, Tang H, Liu Z, Wang J, Wang T, Xu Y, Ji S. Gastrodenol suppresses NLRP3/GSDMD mediated pyroptosis and ameliorates inflammatory diseases. Cellular Immunology 2024, 405: 104888. PMID: 39486308, DOI: 10.1016/j.cellimm.2024.104888.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCytokinesEncephalomyelitis, Autoimmune, ExperimentalFemaleGasderminsHumansInflammasomesInflammationIntracellular Signaling Peptides and ProteinsLipopolysaccharidesMacrophagesMiceMice, Inbred C57BLNLR Family, Pyrin Domain-Containing 3 ProteinPeritonitisPhosphate-Binding ProteinsPyroptosisConceptsNucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3Caspase activationRecruitment domainNLRP3 oligomerizationPyrin domain-containing protein 3Gasdermin D (GSDMD)-mediated pyroptosisProtein 3PyroptosisSecretion of pro-inflammatory cytokinesOligomerizationHydrogen bondsApoptosis-associated speck like proteinInflammatory diseasesTherapeutic strategiesHelicobacter pyloriPro-inflammatory cytokinesCaspaseExperimental autoimmune encephalomyelitisLipopolysaccharide (LPS)-inducedProteinGasderminContext‐specific anti‐inflammatory roles of type III interferon signaling in the lung in nonviral injuries
Feng J, Kim J, Wang V, Chang D, Liu H, Bain W, Robinson K, Jie Z, Kotenko S, Dela Cruz C, Sharma L. Context‐specific anti‐inflammatory roles of type III interferon signaling in the lung in nonviral injuries. Physiological Reports 2024, 12: e70104. PMID: 39455422, PMCID: PMC11511623, DOI: 10.14814/phy2.70104.Peer-Reviewed Original ResearchConceptsIII interferon signalingType III interferon signalingLung injuryInterferon signalingBleomycin-induced weight lossInflammatory responseModel of lung injuryBacterial pathogen Pseudomonas aeruginosaAcute lung injuryPathogen Pseudomonas aeruginosaBacterial endotoxin LPSChemotherapeutic agent bleomycinType III interferonsAnti-inflammatory roleIncreased inflammatory signalingLate time pointsBleomycin modelKnockout miceEndotoxin LPSIII interferonsAntiviral cytokinesDay 3Inflammatory signalingEarly injuryImpaired recoveryMicroglia-mediated neuroimmune suppression in PTSD is associated with anhedonia
Bonomi R, Hillmer A, Woodcock E, Bhatt S, Rusowicz A, Angarita G, Carson R, Davis M, Esterlis I, Nabulsi N, Huang Y, Krystal J, Pietrzak R, Cosgrove K. Microglia-mediated neuroimmune suppression in PTSD is associated with anhedonia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2406005121. PMID: 39172786, PMCID: PMC11363315, DOI: 10.1073/pnas.2406005121.Peer-Reviewed Original ResearchConceptsPTSD groupPrefrontal-limbic circuitsNeuroimmune responseAssociated with anhedoniaPosttraumatic stress disorderPositron emission tomography brain imagingTranslocator protein availabilityBrain immune functionAnhedonic symptomsStress disorderPeripheral immune dysfunctionPTSDGroup differencesSeverity of symptomsPsychiatric diseasesTranslocator proteinBrain imagingAdministration of lipopolysaccharideSymptomsMicroglial markersLPS-induced increaseCompared to controlsImmune functionSickness symptomsAnhedoniaDual function of LapB (YciM) in regulating Escherichia coli lipopolysaccharide synthesis
Shu S, Tsutsui Y, Nathawat R, Mi W. Dual function of LapB (YciM) in regulating Escherichia coli lipopolysaccharide synthesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2321510121. PMID: 38635633, PMCID: PMC11046580, DOI: 10.1073/pnas.2321510121.Peer-Reviewed Original ResearchMeSH KeywordsAmidohydrolasesEscherichia coliEscherichia coli ProteinsLipopolysaccharidesMembrane ProteinsMutationRubredoxinsConceptsLPS synthesisTetratricopeptide repeatCytoplasmic domainLevels of lipopolysaccharideCryo-EM structureGram-negative bacteriaLipopolysaccharide synthesisProtease FtsHRubredoxin domainLpxC activityTransmembrane helicesIn vivo analysisLpxCPseudomonas aeruginosaEnzymatic activityLapBFtsHAllosteric effectsYciMDual functionIn vitroTetratricopeptideAdaptorMotifDeacetylasePositive selection CRISPR screens reveal a druggable pocket in an oligosaccharyltransferase required for inflammatory signaling to NF-κB
Lampson B, Ramίrez A, Baro M, He L, Hegde M, Koduri V, Pfaff J, Hanna R, Kowal J, Shirole N, He Y, Doench J, Contessa J, Locher K, Kaelin W. Positive selection CRISPR screens reveal a druggable pocket in an oligosaccharyltransferase required for inflammatory signaling to NF-κB. Cell 2024, 187: 2209-2223.e16. PMID: 38670073, PMCID: PMC11149550, DOI: 10.1016/j.cell.2024.03.022.Peer-Reviewed Original ResearchConceptsWhole-genome CRISPR-Cas9 screenCRISPR-Cas9 screensCryoelectron microscopy studiesCell surface localizationLipopolysaccharide receptor Toll-like receptor 4OST complexToll-like receptor 4CRISPR screensNF-kBCatalytic subunitN-glycosylationActivate NF-kBBase editorsUncompetitive inhibition mechanismNGI-1Molecular mechanismsCatalytic siteLPS-treated cellsOligosaccharyltransferaseDruggable pocketSTT3AReceptor Toll-like receptor 4Drug mechanism of actionStructural studiesInflammatory signalingLipoarabinomannan mediates localized cell wall integrity during division in mycobacteria
Sparks I, Kado T, Prithviraj M, Nijjer J, Yan J, Morita Y. Lipoarabinomannan mediates localized cell wall integrity during division in mycobacteria. Nature Communications 2024, 15: 2191. PMID: 38467648, PMCID: PMC10928101, DOI: 10.1038/s41467-024-46565-5.Peer-Reviewed Original ResearchConceptsCell wall integrityWall integrityRod cell shapeCell envelope integrityHost-pathogen interactionsCell envelope componentsClinically relevant pathogensAssociated with divisionBiosynthetic mutantsEnvelope integritySubcellular locationMycobacterium smegmatisOld poleMulti-septateCell shapeMutantsBacterial modelRelevant pathogensSeptal placementPhysiological functionsMycobacterium tuberculosisEnvelope componentsMycobacteriaLipoarabinomannanDiderm
2023
Polyinosinic: polycytidylic acid induced inflammation enhances while lipopolysaccharide diminishes alloimmunity to platelet transfusion in mice
Tran J, Muench M, Gaillard B, Darst O, Tomayko M, Jackman R. Polyinosinic: polycytidylic acid induced inflammation enhances while lipopolysaccharide diminishes alloimmunity to platelet transfusion in mice. Frontiers In Immunology 2023, 14: 1281130. PMID: 38146372, PMCID: PMC10749330, DOI: 10.3389/fimmu.2023.1281130.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsHistocompatibility AntigensInflammationLipopolysaccharidesMiceMice, Inbred BALB CPlatelet TransfusionPoly CPoly I-CConceptsB cell responsesPlatelet transfusionsMajor histocompatibility complexCell responsesPrior exposurePlatelet alloimmunizationMemory B cell responsesPlatelet transfusion recipientsSubsequent platelet transfusionsAllogeneic platelet transfusionsNegative bacterial infectionsPolyinosinic-polycytidylic acidGerminal center formationPrior inflammationAlloantibody responsesAlloimmune responsePlatelet refractorinessFuture transplantTransfusion recipientsMHC tetramersAdverse reactionsInflammatory environmentAntigen experiencePlatelet antigensTransfusionUrine and sputum tuberculosis tests: defining the trade-offs in endemic HIV and tuberculosis settings
Wilson D, Cudahy P, Drain P. Urine and sputum tuberculosis tests: defining the trade-offs in endemic HIV and tuberculosis settings. The Lancet Global Health 2023, 11: e809-e810. PMID: 37202010, DOI: 10.1016/s2214-109x(23)00215-2.Commentaries, Editorials and LettersMeSH KeywordsHIV InfectionsHumansLipopolysaccharidesMycobacterium tuberculosisSensitivity and SpecificitySputumTuberculosisTuberculosis, PulmonaryTDAG51 promotes transcription factor FoxO1 activity during LPS‐induced inflammatory responses
Park E, Jeon H, Lee N, Yu J, Park H, Satoh T, Akira S, Furuyama T, Lee C, Choi J, Rho J. TDAG51 promotes transcription factor FoxO1 activity during LPS‐induced inflammatory responses. The EMBO Journal 2023, 42: embj2022111867. PMID: 37203866, PMCID: PMC10308371, DOI: 10.15252/embj.2022111867.Peer-Reviewed Original ResearchMeSH Keywords14-3-3 ProteinsAnimalsEscherichia coliInflammation MediatorsLipopolysaccharidesMiceTranscription FactorsConceptsBone marrow-derived macrophagesInflammatory mediator productionInflammatory responseMediator productionTranscription factor FOXO1Lethal shockLPS-induced inflammatory responseSerum proinflammatory cytokine levelsToll-like receptor (TLR)-mediated inflammatory responsesFoxO1 activitySystemic inflammatory responseProinflammatory cytokine levelsMarrow-derived macrophagesTLR2/4 signaling pathwayFoxO1 nuclear accumulationT cellsCytokine levelsLipopolysaccharide (LPS)-induced inflammatory responsesTDAG51 deficiencyDouble deficiencyLPS-induced inflammatory mediator productionLPS stimulationInnate immunityCytoplasmic translocationLPSIntrinsic B cell TLR-BCR linked coengagement induces class-switched, hypermutated, neutralizing antibody responses in absence of T cells
Rivera C, Zhou Y, Chupp D, Yan H, Fisher A, Simon R, Zan H, Xu Z, Casali P. Intrinsic B cell TLR-BCR linked coengagement induces class-switched, hypermutated, neutralizing antibody responses in absence of T cells. Science Advances 2023, 9: eade8928. PMID: 37115935, PMCID: PMC10146914, DOI: 10.1126/sciadv.ade8928.Peer-Reviewed Original ResearchConceptsClass switch DNA recombinationT cell helpPlasma cell differentiationAntibody responseCell differentiationSomatic hypermutationGeneration of memory B cellsInduce neutralizing antibody responsesAbsence of T cellsMaturation of antibody responsesMemory B cellsNeutralizing antibody responsesResponse to NPDNA recombinationAnamnestic antibody responseMicrobial pathogensFlagellinT cellsB cellsClonal expansionClass switchingProtective antibodiesCoengagementCell receptorsDifferentiationNLRP6 deficiency expands a novel CD103+ B cell population that confers immune tolerance in NOD mice
Pearson J, Peng J, Huang J, Yu X, Tai N, Hu Y, Sha S, Flavell R, Zhao H, Wong F, Wen L. NLRP6 deficiency expands a novel CD103+ B cell population that confers immune tolerance in NOD mice. Frontiers In Immunology 2023, 14: 1147925. PMID: 36911699, PMCID: PMC9995752, DOI: 10.3389/fimmu.2023.1147925.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDiabetes Mellitus, Type 1Immune ToleranceInflammasomesInterleukin-10LipopolysaccharidesMiceMice, Inbred NODConceptsNlrp6-deficient miceType 1 diabetesNLRP6 deficiencyB cellsIL-10Non-obese diabetic (NOD) miceType 1 diabetes developmentRole of NLRP6Germ-free miceT cell proliferationB cell populationsIntestinal epithelial cellsBreg populationAutoimmune diabetesNOD miceCrohn's diseaseImmune toleranceDiabetes developmentDiabetic miceImmune cellsCD103Inflammasome proteinsImmune responseNLRP6Gut microbiotaThe Effects of Pregnancy on the Pulmonary Immune Response in a Mouse Model of LPS-Induced Acute Lung Injury
Rieck R, Bivona J, Hoyt L, Ventrone S, Kokoszynska M, Bonney E, Suratt B. The Effects of Pregnancy on the Pulmonary Immune Response in a Mouse Model of LPS-Induced Acute Lung Injury. American Journal Of Perinatology 2023, 40: 817-824. PMID: 36796402, DOI: 10.1055/s-0043-1761916.Peer-Reviewed Original ResearchConceptsAcute lung injuryEffect of pregnancyNonpregnant miceAdhesion molecule-1Lung injuryPregnant miceNeutrophil responseImmune responseVCAM-1Mouse modelBronchoalveolar lavage fluid (BALF) differential cell countMolecule-1LPS-Induced Acute Lung InjuryPulmonary innate immune responseVascular cell adhesion molecule-1Intercellular adhesion molecule-1Cell adhesion molecule-1BALF total cellsBlood neutrophil responsesInhalation of lipopolysaccharidePulmonary immune responseVascular endothelial adhesion moleculesSevere lung diseasePeripheral blood neutrophilsBone marrow neutrophilsSHANK3 in vagal sensory neurons regulates body temperature, systemic inflammation, and sepsis
Zhang L, Bang S, He Q, Matsuda M, Luo X, Jiang Y, Ji R. SHANK3 in vagal sensory neurons regulates body temperature, systemic inflammation, and sepsis. Frontiers In Immunology 2023, 14: 1124356. PMID: 36845137, PMCID: PMC9944123, DOI: 10.3389/fimmu.2023.1124356.Peer-Reviewed Original ResearchConceptsVagal sensory neuronsNodose ganglionSensory neuronsSystemic inflammationBody temperatureDorsal root ganglion sensory neuronsSerum IL-6 levelsAuricular vagus nerve stimulationBasal core temperatureIL-6 levelsVagus nerve stimulationAutism spectrum disorderRole of Shank3Conditional knockout miceSynaptic scaffolding proteinsSepsis mortalityNerve stimulationExcessive inflammationHeat painInflammation dysregulationKO miceKnockout miceInflammationSHANK3 expressionNovel molecular mechanism
2022
Systemic inflammation enhances stimulant-induced striatal dopamine elevation in tobacco smokers
Zakiniaeiz Y, Hoye J, Ryan Petrulli J, LeVasseur B, Stanley G, Gao H, Najafzadeh S, Ropchan J, Nabulsi N, Huang Y, Chen MK, Matuskey D, Barron DS, Kelmendi B, Fulbright RK, Hampson M, Cosgrove KP, Morris ED. Systemic inflammation enhances stimulant-induced striatal dopamine elevation in tobacco smokers. Brain Behavior And Immunity 2022, 106: 262-269. PMID: 36058419, PMCID: PMC10097458, DOI: 10.1016/j.bbi.2022.08.016.Peer-Reviewed Original ResearchConceptsEffects of LPSDopamine elevationTobacco smokersHealthy controlsSystemic inflammationDopamine systemImmune-brain interactionReward-related brain regionsAdministration of placeboAdministration of LPSSmoking statusRepeated-measures ANOVAPathophysiology of addictionDrug dosingPlaceboIndependent cohortSmokersDrug reinforcementEffect size determinationImmune systemRandomized orderBrain regionsLPSMethylphenidatePBO conditionRegulatory mechanisms of lipopolysaccharide synthesis in Escherichia coli
Shu S, Mi W. Regulatory mechanisms of lipopolysaccharide synthesis in Escherichia coli. Nature Communications 2022, 13: 4576. PMID: 35931690, PMCID: PMC9356133, DOI: 10.1038/s41467-022-32277-1.Peer-Reviewed Original ResearchMeSH KeywordsAmidohydrolasesEscherichia coliEscherichia coli ProteinsGram-Negative BacteriaLipopolysaccharidesMembrane ProteinsConceptsRegulatory mechanismsAnti-adaptor proteinsFirst committed stepMost Gram-negative bacteriaEssential glycolipidEssential membraneGram-negative bacteriaTransmembrane helicesAdaptor proteinCommitted stepCytoplasmic domainFtsHLPS synthesisAnalysis unravelsLipopolysaccharide synthesisLapBEscherichia coliE. coliPermeability barrierProtein levelsLpxCProtease activityProteinColiYejM
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