Featured Publications
Fexofenadine inhibits TNF signaling through targeting to cytosolic phospholipase A2 and is therapeutic against inflammatory arthritis
Liu R, Chen Y, Fu W, Wang S, Cui Y, Zhao X, Lei Z, Hettinghouse A, Liu J, Wang C, Zhang C, Bi Y, Xiao G, Chen Z, Liu C. Fexofenadine inhibits TNF signaling through targeting to cytosolic phospholipase A2 and is therapeutic against inflammatory arthritis. Annals Of The Rheumatic Diseases 2019, 78: 1524. PMID: 31302596, PMCID: PMC8157820, DOI: 10.1136/annrheumdis-2019-215543.Peer-Reviewed Original ResearchConceptsAnti-TNF activityCytosolic phospholipase A2Inflammatory arthritisTNF-α transgenic miceInflammatory arthritis modelInflammatory rheumatic diseasesCollagen-induced arthritisAnti-inflammatory activityPhospholipase A2New therapeutic interventionsActivated B cellsTNF-α signalingNecrosis factor-alpha signalingDrug affinity responsive target stabilityDBA/1 miceRheumatic diseasesArthritis modelAutoimmune diseasesCellular thermal shiftSerial screeningB cellsTransgenic miceArthritisDrug AdministrationTherapeutic interventionsThe Growth Factor Progranulin Binds to TNF Receptors and Is Therapeutic Against Inflammatory Arthritis in Mice
Tang W, Lu Y, Tian QY, Zhang Y, Guo FJ, Liu GY, Syed NM, Lai Y, Lin EA, Kong L, Su J, Yin F, Ding AH, Zanin-Zhorov A, Dustin ML, Tao J, Craft J, Yin Z, Feng JQ, Abramson SB, Yu XP, Liu CJ. The Growth Factor Progranulin Binds to TNF Receptors and Is Therapeutic Against Inflammatory Arthritis in Mice. Science 2011, 332: 478-484. PMID: 21393509, PMCID: PMC3104397, DOI: 10.1126/science.1199214.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAnimalsAnti-Inflammatory Agents, Non-SteroidalArthritis, ExperimentalCartilage, ArticularFemaleGranulinsHumansIntercellular Signaling Peptides and ProteinsLigandsMaleMiceMice, Inbred StrainsMice, KnockoutMice, TransgenicMiddle AgedProgranulinsProtein Interaction Domains and MotifsReceptors, Tumor Necrosis Factor, Type IReceptors, Tumor Necrosis Factor, Type IIRecombinant Fusion ProteinsRecombinant ProteinsSignal TransductionT-Lymphocytes, RegulatoryTumor Necrosis Factor-alphaYoung AdultConceptsInflammatory arthritisAdministration of progranulinAntagonist of TNFαCollagen-induced arthritisArthritis mouse modelPGRN-deficient miceNew potential therapeutic interventionsPotential therapeutic interventionsGrowth factor progranulinNecrosis factor receptorRheumatoid arthritisMouse modelArthritisTherapeutic interventionsProgranulinTNF receptorFactor receptorMiceReceptorsInflammationTissue repairTNFαIntracellular signalingAtsttrinTNFR
2024
Novel peptide inhibitor of human tumor necrosis factor-α has antiarthritic activity
Sahu D, Gupta C, Yennamalli R, Sharma S, Roy S, Hasan S, Gupta P, Sharma V, Kashyap S, Kumar S, Dwivedi V, Zhao X, Panda A, Das H, Liu C. Novel peptide inhibitor of human tumor necrosis factor-α has antiarthritic activity. Scientific Reports 2024, 14: 12935. PMID: 38839973, PMCID: PMC11153517, DOI: 10.1038/s41598-024-63790-6.Peer-Reviewed Original ResearchConceptsProtein-protein interactionsGel mobility-shift assaysCollagen-induced arthritisMobility-shift assaysCell surface receptorsFluorescence-activated cell sortingSequence strandsBinding of TNFIn silico methodsCell deathMouse modelSurface receptorsNuclear translocationTrimer formationCell culture assaysRheumatoid arthritisVicious cycle of inflammationModel of collagen-induced arthritisTumor necrosis factor-aCell sortingMouse model of collagen-induced arthritisA549 cellsCycle of inflammationInflammatory bone destructionCulture assay
2023
Tau deficiency inhibits classically activated macrophage polarization and protects against collagen-induced arthritis in mice
Chen M, Fu W, Xu H, Liu C. Tau deficiency inhibits classically activated macrophage polarization and protects against collagen-induced arthritis in mice. Arthritis Research & Therapy 2023, 25: 146. PMID: 37559125, PMCID: PMC10410869, DOI: 10.1186/s13075-023-03133-4.Peer-Reviewed Original ResearchConceptsInflammatory cell infiltrationPro-inflammatory cytokinesRheumatoid arthritisAnkle jointSerum levelsCell infiltrationMacrophage polarizationOsteoclast activityCartilage damagePathogenesis of RACollagen-induced arthritis modelTau-/- miceCollagen-induced arthritisInflammatory joint diseasePro-inflammatory functionsProgression of CIAPotential therapeutic targetRole of tauInflammatory arthritisBone erosionArthritis incidenceBone lossClinical scoresArthritis modelInflammatory disorders
2022
Penfluridol targets acid sphingomyelinase to inhibit TNF signaling and is therapeutic against inflammatory autoimmune diseases
Chen Y, Liu R, Cui Y, Hettinghouse A, Fu W, Zhang L, Zhang C, Liu C. Penfluridol targets acid sphingomyelinase to inhibit TNF signaling and is therapeutic against inflammatory autoimmune diseases. Arthritis Research & Therapy 2022, 24: 27. PMID: 35045889, PMCID: PMC8767691, DOI: 10.1186/s13075-021-02713-6.Peer-Reviewed Original ResearchConceptsInflammatory autoimmune diseaseAnti-TNF activityNF-κB activationInflammatory arthritisAutoimmune diseasesAcid sphingomyelinase activityTherapeutic effectTumor necrosis factor αInhibitory effectTNFα-transgenic miceCollagen-induced arthritisSeverity of arthritisInflammatory cytokine productionM1 macrophage polarizationBone marrow-derived macrophagesNecrosis factor αNF-κB activitySphingomyelinase activitySmall molecule drug libraryRAW 264.7 macrophage cell lineMarrow-derived macrophagesAcid sphingomyelinaseDrug affinity responsive target stabilityCytokine productionChronic schizophrenia
2020
In Vitro Physical and Functional Interaction Assays to Examine the Binding of Progranulin Derivative Atsttrin to TNFR2 and Its Anti-TNFα Activity
Fu W, Hettinghouse A, Liu C. In Vitro Physical and Functional Interaction Assays to Examine the Binding of Progranulin Derivative Atsttrin to TNFR2 and Its Anti-TNFα Activity. Methods In Molecular Biology 2020, 2248: 109-119. PMID: 33185871, PMCID: PMC8112733, DOI: 10.1007/978-1-0716-1130-2_8.Peer-Reviewed Original ResearchConceptsAnti-TNFα activityAutoimmune diseasesTartrate-resistant acid phosphatase (TRAP) stainingAnti-TNFα therapyCollagen-induced arthritisInflammatory disease modelsGood therapeutic effectAcid phosphatase stainingGrowth factor-like moleculesTNF inhibitorsTherapeutic effectTNFα activityProgranulinFunctional inhibitionTNFR2AtsttrinDisease modelsPhosphatase stainingTNFRTNFαDiseaseInhibitionCritical roleDirect bindingHigh affinity
2016
Foxo4‐ and Stat3‐dependent IL‐10 production by progranulin in regulatory T cells restrains inflammatory arthritis
Fu W, Hu W, Shi L, Mundra J, Xiao G, Dustin M, Liu C. Foxo4‐ and Stat3‐dependent IL‐10 production by progranulin in regulatory T cells restrains inflammatory arthritis. The FASEB Journal 2016, 31: 1354-1367. PMID: 28011648, PMCID: PMC5349791, DOI: 10.1096/fj.201601134r.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArthritis, ExperimentalCell Cycle ProteinsCells, CulturedForkhead Transcription FactorsGranulinsIntercellular Signaling Peptides and ProteinsInterleukin-10MAP Kinase Signaling SystemMiceMice, Inbred DBAPhosphatidylinositol 3-KinasesProgranulinsSTAT3 Transcription FactorT-Lymphocytes, RegulatoryConceptsIL-10 productionRegulatory T cellsInflammatory arthritisIL-10T cellsAnti-inflammatory cytokine IL-10Forkhead box protein O4PI3K pathwayCollagen-induced arthritisCytokine IL-10Green fluorescent protein reporter miceTranscription factorsSequencing screenSignal transducerJNK signalingTranscription 3K pathwayImmunological mechanismsAutoimmune diseasesInflammatory conditionsMouse modelArthritisPresent new insightsReporter miceProgranulin
2014
Selective oral ROCK2 inhibitor down-regulates IL-21 and IL-17 secretion in human T cells via STAT3-dependent mechanism
Zanin-Zhorov A, Weiss J, Nyuydzefe M, Chen W, Scher J, Mo R, Depoil D, Rao N, Liu B, Wei J, Lucas S, Koslow M, Roche M, Schueller O, Weiss S, Poyurovsky M, Tonra J, Hippen K, Dustin M, Blazar B, Liu C, Waksal S. Selective oral ROCK2 inhibitor down-regulates IL-21 and IL-17 secretion in human T cells via STAT3-dependent mechanism. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 16814-16819. PMID: 25385601, PMCID: PMC4250132, DOI: 10.1073/pnas.1414189111.Peer-Reviewed Original ResearchConceptsT cellsIL-17IL-21Forkhead box P3 (Foxp3) expressionRegulatory T cell subsetsPhase 1 clinical trialCollagen-induced arthritisIL-17 secretionRegulatory T cellsRheumatoid arthritis patientsTreatment of autoimmunityBox P3 expressionT cell subsetsDevelopment of autoimmunityROCK2 inhibitorIFN regulatory factor 4Healthy human subjectsT cell receptor stimulationIL-21 promoterSTAT3-dependent mechanismRegulatory factor 4Human T cellsArthritis patientsSiRNA-mediated inhibitionProinflammatory cytokines
2012
Enhanced COMP catabolism detected in serum of patients with arthritis and animal disease models through a novel capture ELISA
Lai Y, Yu X, Zhang Y, Tian Q, Song H, Mucignat M, Perris R, Samuels J, Krasnokutsky S, Attur M, Greenberg J, Abramson S, Di Cesare P, Liu C. Enhanced COMP catabolism detected in serum of patients with arthritis and animal disease models through a novel capture ELISA. Osteoarthritis And Cartilage 2012, 20: 854-862. PMID: 22595227, PMCID: PMC3389204, DOI: 10.1016/j.joca.2012.05.003.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAnimalsAntirheumatic AgentsArthritis, ExperimentalArthritis, RheumatoidCartilage Oligomeric Matrix ProteinCase-Control StudiesEnzyme-Linked Immunosorbent AssayExtracellular Matrix ProteinsFemaleGlycoproteinsHumansMaleMatrilin ProteinsMethotrexateMiceMice, TransgenicMiddle AgedOsteoarthritisRecombinant Fusion ProteinsSynovial FluidTumor Necrosis Factor-alphaYoung AdultConceptsCollagen-induced arthritisEnzyme-linked immunosorbent assayCapture enzyme-linked immunosorbent assayCOMP fragmentsRA patientsOA patientsRheumatoid arthritisRodent arthritis modelsTherapeutic response predictorsArthritis mouse modelSera of patientsTNF-transgenic miceTransgenic animal modelsEffects of interventionsNovel sandwich enzyme-linked immunosorbent assayAnimal disease modelsSandwich enzyme-linked immunosorbent assayDisease courseSerum levelsArthritis modelTNFα inhibitorsArthritic patientsCOMP levelsMurine modelResponse predictors
2011
Progranulin: A growth factor, a novel TNFR ligand and a drug target
Liu C, Bosch X. Progranulin: A growth factor, a novel TNFR ligand and a drug target. Pharmacology & Therapeutics 2011, 133: 124-132. PMID: 22008260, PMCID: PMC4429904, DOI: 10.1016/j.pharmthera.2011.10.003.Peer-Reviewed Original ResearchConceptsGrowth factorAdministration of progranulinCollagen-induced arthritisAnti-inflammatory effectsArthritis mouse modelAnti-inflammatory propertiesExact molecular pathwaysInflammatory arthritisRheumatoid arthritisNeurotrophic factorArthritic processImmune cellsNecrosis factorMouse modelTNFR ligandsProgranulinFrontotemporal dementiaPGRN proteinArthritisPGRN geneExperimental modelCancer cellsCrucial mediatorEpithelial cellsChondrogenic growth factors