2019
Ruxolitinib, a selective JAK1/2 inhibitor, for the treatment of serious diseases caused by Staphylococcus aureus superantigens
Carnes H, Mehrkens B, Stegman M, Rajagopalan G. Ruxolitinib, a selective JAK1/2 inhibitor, for the treatment of serious diseases caused by Staphylococcus aureus superantigens. The Journal Of Immunology 2019, 202: 190.34-190.34. DOI: 10.4049/jimmunol.202.supp.190.34.Peer-Reviewed Original ResearchSystemic inflammatory response syndromeMulti-organ failureT cellsHLA-DR3 transgenic miceHLA class II moleculesVehicle-treated miceVivo studiesInflammatory response syndromeT cell subsetsToxic shock syndromeJAK 1/2 inhibitorSelective JAK1/2 inhibitorClass II moleculesStaphylococcus aureusDose-dependent mannerSerious diseaseJanus kinaseIL-17Response syndromeOrgan failureJAK1/2 inhibitorActivation markersCell subsetsShock syndromeIL-2
2018
Dissecting the pathogenic versus protective roles of IFN-γ and IL-17 in staphylococcal toxic shock syndrome and pneumonia using gene targeted HLA-DR3 transgenic mice
Rajagopalan G, Krogman A, Chowdhary V. Dissecting the pathogenic versus protective roles of IFN-γ and IL-17 in staphylococcal toxic shock syndrome and pneumonia using gene targeted HLA-DR3 transgenic mice. The Journal Of Immunology 2018, 200: 117.3-117.3. DOI: 10.4049/jimmunol.200.supp.117.3.Peer-Reviewed Original ResearchHLA-DR3 transgenic miceToxic shock syndromeIL-17Transgenic miceHLA-DR3Shock syndromeAdaptive T cell responsesStaphylococcal toxic shock syndromeIL-17 family membersT cell responsesRole of IFNStaphylococcus aureus infectionS. aureusNon-specific activationTh17 cellsSerum levelsHLA-DRMice succumbedSystemic elevationTh1 cellsAureus infectionTissue injuryT cellsInfectious agentsIFN
2014
Systemic Inflammatory Response Elicited by Superantigen Destabilizes T Regulatory Cells, Rendering Them Ineffective during Toxic Shock Syndrome
Tilahun AY, Chowdhary VR, David CS, Rajagopalan G. Systemic Inflammatory Response Elicited by Superantigen Destabilizes T Regulatory Cells, Rendering Them Ineffective during Toxic Shock Syndrome. The Journal Of Immunology 2014, 193: 2919-2930. PMID: 25092888, PMCID: PMC4157092, DOI: 10.4049/jimmunol.1400980.Peer-Reviewed Original ResearchMeSH KeywordsAdoptive TransferAnimalsAntibodiesAntigen-Antibody ComplexEnterotoxinsGlucocorticoid-Induced TNFR-Related ProteinGlucocorticoidsHLA-DR alpha-ChainsHLA-DR beta-ChainsHLA-DR3 AntigenInterferon-gammaInterleukin-17Interleukin-2Lymphocyte ActivationMethicillin-Resistant Staphylococcus aureusMiceMice, TransgenicReceptors, Tumor Necrosis FactorShock, SepticStaphylococcal InfectionsSuperantigensT-Lymphocytes, RegulatoryUp-RegulationConceptsToxic shock syndromeEndogenous TregsRegulatory cellsShock syndromeT cellsGlucocorticoid-induced TNFR family-related receptorCommunity-acquired methicillin-resistant strainsEx vivoHLA-DR3 transgenic miceSerum IFN-γ levelsFailure of TregsSystemic inflammatory responseIL-2/T regulatory (Treg) cellsIFN-γ levelsConventional T cellsLife-threatening infectionsMethicillin-resistant strainsT cell activationS. aureus strainsTreg numbersAdoptive transferIL-17Immune activationInflammatory responseThe Impact of Staphylococcus aureus‐Associated Molecular Patterns on Staphylococcal Superantigen‐Induced Toxic Shock Syndrome and Pneumonia
Tilahun A, Karau M, Ballard A, Gunaratna M, Thapa A, David C, Patel R, Rajagopalan G. The Impact of Staphylococcus aureus‐Associated Molecular Patterns on Staphylococcal Superantigen‐Induced Toxic Shock Syndrome and Pneumonia. Mediators Of Inflammation 2014, 2014: 468285. PMID: 25024509, PMCID: PMC4082930, DOI: 10.1155/2014/468285.Peer-Reviewed Original ResearchConceptsPathogen-associated molecular patternsHLA-DQ8 transgenic miceHeat-killed Staphylococcus aureusToxic shock syndromeStaphylococcal superantigensHLA-DR3Shock syndromeMolecular patternsTransgenic miceS. aureus-derived peptidoglycanSerious S. aureus infectionsCytokine/chemokine responsesLipoteichoic acidStaphylococcal toxic shock syndromeS. aureusLife-threatening systemic diseaseAnti-inflammatory roleT cell expansionS. aureus infectionT cell proliferationToxigenic S. aureusStaphylococcus aureusAdaptive immune systemChemokine responsesSystemic disease
2012
Detrimental effects of T regulatory cell-promoting IL-2-anti-IL-2 complexes in staphylococcal toxic shock syndrome. (164.13)
Rajagopalan G, Tilahun A. Detrimental effects of T regulatory cell-promoting IL-2-anti-IL-2 complexes in staphylococcal toxic shock syndrome. (164.13). The Journal Of Immunology 2012, 188: 164.13-164.13. DOI: 10.4049/jimmunol.188.supp.164.13.Peer-Reviewed Original ResearchToxic shock syndromeHLA-DR3 transgenic miceTreg numbersShock syndromeNon-menstrual toxic shock syndromeTransgenic miceCytokine/chemokine stormStaphylococcal toxic shock syndromeNumber of TregsMultiple organ failureStaphylococcal enterotoxin BChemokine stormMIP-1βOrgan failureMIP-1αUntreated groupSuperantigen exotoxinsDay 5Immune systemDay 0IL2CMiceEnterotoxin BStreptococcus pyogenesAdministration
2011
Chimeric Anti-Staphylococcal Enterotoxin B Antibodies and Lovastatin Act Synergistically to Provide In Vivo Protection against Lethal Doses of SEB
Tilahun M, Kwan A, Natarajan K, Quinn M, Tilahun A, Xie C, Margulies D, Osborne B, Goldsby R, Rajagopalan G. Chimeric Anti-Staphylococcal Enterotoxin B Antibodies and Lovastatin Act Synergistically to Provide In Vivo Protection against Lethal Doses of SEB. PLOS ONE 2011, 6: e27203. PMID: 22102880, PMCID: PMC3216929, DOI: 10.1371/journal.pone.0027203.Peer-Reviewed Original ResearchConceptsToxic shock syndromeLethal toxic shock syndromeHLA-DR3 transgenic miceStaphylococcal enterotoxin BChimeric human-mouse antibodyShock syndromeT cellsVivo protectionTransgenic micePartial protectionComplete protectionLethal dosesT cell populationsClass II MHCSignificant partial protectionAnti-SEB antibodiesHuman T cellsOnly partial protectionInflammatory cytokinesClinical safetyII MHCB antibodiesVivo modelChimeric antibodyEnterotoxin BHuman Leukocyte Antigen Class II Transgenic Mouse Model Unmasks the Significant Extrahepatic Pathology in Toxic Shock Syndrome
Tilahun A, Marietta E, Wu T, Patel R, David C, Rajagopalan G. Human Leukocyte Antigen Class II Transgenic Mouse Model Unmasks the Significant Extrahepatic Pathology in Toxic Shock Syndrome. American Journal Of Pathology 2011, 178: 2760-2773. PMID: 21641398, PMCID: PMC3124354, DOI: 10.1016/j.ajpath.2011.02.033.Peer-Reviewed Original ResearchConceptsToxic shock syndromeShock syndromeTransgenic miceSmall intestineHLA-DR3 transgenic miceHLA class II moleculesMultiple organ inflammationPotent T cell activatorsKey pathogenic eventClass II moleculesT cell activatorsGut dysfunctionKawasaki diseaseLiver failureHeavy infiltrationHigh morbidityD-GalN.Pathologic changesT lymphocytesExtrahepatic pathologyPathogenic eventsAbsorptive functionD-galactosamineSensitization modelMouse strainsInterferon Gamma-Dependent Intestinal Pathology Contributes to the Lethality in Bacterial Superantigen-Induced Toxic Shock Syndrome
Tilahun A, Holz M, Wu T, David C, Rajagopalan G. Interferon Gamma-Dependent Intestinal Pathology Contributes to the Lethality in Bacterial Superantigen-Induced Toxic Shock Syndrome. PLOS ONE 2011, 6: e16764. PMID: 21304813, PMCID: PMC3033413, DOI: 10.1371/journal.pone.0016764.Peer-Reviewed Original ResearchConceptsToxic shock syndromeTransgenic miceShock syndromePathogenesis of TSSSmall intestineLethal toxic shock syndromeHLA-DR3 transgenic miceSystematic histopathological examinationSystemic cytokine stormMultiple organ dysfunctionRobust T cell activationSevere inflammatory changesSmall bowel pathologyT cell expansionAnti-inflammatory propertiesSignificant pathological changesT cell activationIFN-γ geneGut permeabilityCytokine stormSEB challengeBowel pathologyInflammatory changesOrgan dysfunctionIntestinal pathology
2010
Detrimental Effect of the Proteasome Inhibitor, Bortezomib in Bacterial Superantigen- and Lipopolysaccharide-induced Systemic Inflammation
Tilahun A, Theuer J, Patel R, David C, Rajagopalan G. Detrimental Effect of the Proteasome Inhibitor, Bortezomib in Bacterial Superantigen- and Lipopolysaccharide-induced Systemic Inflammation. Molecular Therapy 2010, 18: 1143-1154. PMID: 20372109, PMCID: PMC2889741, DOI: 10.1038/mt.2010.53.Peer-Reviewed Original ResearchConceptsToxic shock syndromeStaphylococcal enterotoxin BNF-kappaB activationSystemic inflammationSerum levelsBacterial superantigensKappaB activationElevated TNF-alpha levelsTNF-alpha levelsAcute liver failureProteasome inhibitorsSevere systemic inflammationNuclear factor-kappaBSerum biochemical parametersTNF-alpha-induced cell deathSerum TNFLiver failureHistopathological findingsUntreated miceShock syndromeProphylactic useMurine modelImportant cytokineBortezomibFactor-kappaB
2009
Therapeutic use of proteasome inhibitors in bacterial superantigen- and LPS-induced acute systemic inflammatory response syndromes (93.13)
rajagopalan G, Tilahun A, David C. Therapeutic use of proteasome inhibitors in bacterial superantigen- and LPS-induced acute systemic inflammatory response syndromes (93.13). The Journal Of Immunology 2009, 182: 93.13-93.13. DOI: 10.4049/jimmunol.182.supp.93.13.Peer-Reviewed Original ResearchToxic shock syndromeAcute systemic inflammatory response syndromeHLA class II transgenic miceProfound systemic inflammatory responseSystemic inflammatory response syndromeTherapeutic useAcute systemic inflammatory diseaseII transgenic miceInflammatory response syndromeSystemic inflammatory diseaseSystemic inflammatory responseAcute liver failureProteasome inhibitorsPro-inflammatory cytokinesT cell activationSerum biochemical parametersStaphylococcal enterotoxin BPro-apoptotic effectsLiver failureResponse syndromeSerum levelsHistopathological findingsCytokine productionSepsis modelShock syndromeEarly gene expression changes induced by the bacterial superantigen staphylococcal enterotoxin B and its modulation by a proteasome inhibitor
Rajagopalan G, Tilahun A, Asmann Y, David C. Early gene expression changes induced by the bacterial superantigen staphylococcal enterotoxin B and its modulation by a proteasome inhibitor. Physiological Genomics 2009, 37: 279-293. PMID: 19336531, PMCID: PMC2685500, DOI: 10.1152/physiolgenomics.90385.2008.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBoronic AcidsBortezomibCytokinesEnterotoxinsGene Expression ProfilingGene Expression RegulationHLA-DR alpha-ChainsHLA-DR AntigensInflammation MediatorsMiceMice, TransgenicOligonucleotide Array Sequence AnalysisProtease InhibitorsPyrazinesReceptors, ChemokineReceptors, CytokineSignal TransductionSuperantigensConceptsToxic shock syndromePathogenesis of TSSStaphylococcal enterotoxin BBacterial superantigen staphylococcal enterotoxin BSuperantigen staphylococcal enterotoxin BEnterotoxin BAdministration of bortezomibAnti-inflammatory mediatorsTh17-type cytokinesProteasome inhibitorsCytokines/chemokinesSerious systemic illnessTransgenic mouse modelSuitable animal modelEarly gene expression changesNF-kappaB pathwaySystemic illnessSerum levelsShock syndromeImmunoregulatory cytokinesBacterial superantigensCC chemokinesMouse modelVivo administrationAnimal models
2008
CYCLOOXYGENASE 2 PATHWAY AND ITS THERAPEUTIC INHIBITION IN SUPERANTIGEN-INDUCED TOXIC SHOCK
Rajagopalan G, Asmann Y, Lytle A, Tilahun A, Theuer J, Smart M, Patel R, David C. CYCLOOXYGENASE 2 PATHWAY AND ITS THERAPEUTIC INHIBITION IN SUPERANTIGEN-INDUCED TOXIC SHOCK. Shock 2008, 30: 721-728. PMID: 18496243, DOI: 10.1097/shk.0b013e31817048f7.Peer-Reviewed Original ResearchConceptsToxic shock syndromeTherapeutic inhibitionAcute systemic inflammatory responseSevere toxic shock syndromeCytokine/chemokine productionT-cell activation/proliferationPotent T cell activatorsStrong immune activationMultiple organ dysfunctionSystemic inflammatory responseCOX-2 pathwayTransgenic mouse modelActivation/proliferationT cell activatorsT cell activationAgent of bioterrorismOrgan dysfunctionChemokine productionImmune activationFamily of exotoxinsShock syndromeEffective therapyInflammatory responseMicroarray-based gene expression profilingCOX-2Regulatory T cells and superantigen‐induced toxic shock. A study using HLA class II transgenic mice
Rajagopalan G, Epstein B, Lytle A, David C. Regulatory T cells and superantigen‐induced toxic shock. A study using HLA class II transgenic mice. The FASEB Journal 2008, 22: 848.11-848.11. DOI: 10.1096/fasebj.22.1_supplement.848.11.Peer-Reviewed Original ResearchToxic shock syndromeRegulatory T cellsHLA-DR3 transgenic miceT cellsTransgenic miceHLA class II transgenic miceDepletion of TregsII transgenic miceSerum cytokine levelsStaphylococcal enterotoxin BTreg cellsCytokine levelsIL-17Regulatory cellsSEB challengeIL-21IL-22Systemic exposureIL-6Shock syndromeIL-2IL-2RSplenic expressionTGF-b1Toxic shock
2007
Chronic low-grade exposure to bacterial superantigens elicits sustained T cell expansion and multiorgan inflammation. Implications for autoimmunity. (130.22)
Rajagopalan G, Smart M, Grande J, David C. Chronic low-grade exposure to bacterial superantigens elicits sustained T cell expansion and multiorgan inflammation. Implications for autoimmunity. (130.22). The Journal Of Immunology 2007, 178: s232-s232. DOI: 10.4049/jimmunol.178.supp.130.22.Peer-Reviewed Original ResearchBacterial superantigensT cellsChronic exposureHLA-DQ8 transgenic miceIntense perivascular infiltrationLow-grade exposurePercentage of CD8MHC class II moleculesAntigen non-specific mannerT cell expansionToxic shock syndromeMHC class IITransgenic mouse modelClass II moleculesMurine MHC class IIPerivascular infiltrationHLA-DR3Inflammatory infiltrateMiniosmotic pumpsShock syndromeImmunological outcomesAcute diseaseMultiorgan inflammationHistological examinationMouse model
2006
Acute systemic immune activation following vaginal exposure to staphylococcal enterotoxin B—Implications for menstrual shock
Rajagopalan G, Smart M, Murali N, Patel R, David C. Acute systemic immune activation following vaginal exposure to staphylococcal enterotoxin B—Implications for menstrual shock. Journal Of Reproductive Immunology 2006, 73: 51-59. PMID: 17070600, DOI: 10.1016/j.jri.2006.06.007.Peer-Reviewed Original ResearchConceptsMenstrual toxic shock syndromeSystemic immune activationHLA class II transgenic miceStaphylococcal enterotoxin BII transgenic miceImmune activationToxic shock syndromeSuperantigenic exotoxinsShock syndromeVaginal administrationTransgenic miceAcute systemic inflammatory diseaseSystemic inflammatory diseaseToxic shock syndrome toxinPeripheral lymphoid organsSEB-reactiveVaginal exposureProinflammatory cytokinesConjunctival routeLeukocytic infiltrationProfound elevationInflammatory diseasesLymphoid organsStaphylococcal superantigensT cells