2017
Passive therapy with humanized anti-staphylococcal enterotoxin B antibodies attenuates systemic inflammatory response and protects from lethal pneumonia caused by staphylococcal enterotoxin B-producing Staphylococcus aureus
Karau M, Tilahun M, Krogman A, Osborne B, Goldsby R, David C, Mandrekar J, Patel R, Rajagopalan G. Passive therapy with humanized anti-staphylococcal enterotoxin B antibodies attenuates systemic inflammatory response and protects from lethal pneumonia caused by staphylococcal enterotoxin B-producing Staphylococcus aureus. Virulence 2017, 8: 1148-1159. PMID: 27925510, PMCID: PMC5711449, DOI: 10.1080/21505594.2016.1267894.Peer-Reviewed Original ResearchConceptsHLA-DR3 transgenic miceSystemic inflammatory responseOnset of infectionLethal pneumoniaTransgenic miceInflammatory responseB antibodiesHLA class II transgenic miceStrong systemic immune responsePolyclonal human IgGII transgenic miceRobust T cell activationSystemic immune responsesPro-inflammatory cytokinesLethal toxic shockAnti-toxin antibodiesToxigenic Staphylococcus aureusHuman IgGS. aureusStaphylococcus aureusT cell activationAnti-SEB antibodiesStaphylococcal enterotoxin BConventional mouse strainsProphylactic administration
2012
The impact of tacrolimus on the immunopathogenesis of staphylococcal enterotoxin-induced systemic inflammatory response syndrome and pneumonia
Tilahun A, Karau M, Clark C, Patel R, Rajagopalan G. The impact of tacrolimus on the immunopathogenesis of staphylococcal enterotoxin-induced systemic inflammatory response syndrome and pneumonia. Microbes And Infection 2012, 14: 528-536. PMID: 22273732, DOI: 10.1016/j.micinf.2012.01.001.Peer-Reviewed Original ResearchConceptsStaphylococcal superantigensT cell activationChemokine levelsCell activationSystemic inflammatory response syndromeDR3 transgenic miceEfficacy of tacrolimusInflammatory response syndromeHuman leukocyte antigenImpact of tacrolimusPotent immunosuppressive agentPost-exposure treatmentT cell proliferationS. aureus strainsSystemic cytokinesGut dysfunctionSerum cytokinesResponse syndromeImmunosuppressive agentsLeukocyte antigenSystemic pathologyTacrolimusLethal pneumoniaPneumoniaTransgenic mice
2011
Human 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-kappaBPotent Neutralization of Staphylococcal Enterotoxin B by Synergistic Action of Chimeric Antibodies
Tilahun M, Rajagopalan G, Shah-Mahoney N, Lawlor R, Tilahun A, Xie C, Natarajan K, Margulies D, Ratner D, Osborne B, Goldsby R. Potent Neutralization of Staphylococcal Enterotoxin B by Synergistic Action of Chimeric Antibodies. Infection And Immunity 2010, 78: 2801-2811. PMID: 20308304, PMCID: PMC2876561, DOI: 10.1128/iai.01121-09.Peer-Reviewed Original ResearchConceptsStaphylococcal enterotoxin BT cell receptorT cell populationsT cell activationHLA-DR3 transgenic miceMouse mAbsHuman peripheral blood mononuclear cellsPeripheral blood mononuclear cellsEnterotoxin BCross-linking T-cell receptorsAntigen-independent proliferationClass II major histocompatibility complex moleculesBlood mononuclear cellsAntigen-presenting cellsChimeric human-mouse antibodyMajor histocompatibility complex moleculesT cell proliferationAntigen-independent activationHistocompatibility complex moleculesAnti-SEB antibodiesCytokine productionMononuclear cellsCytokine secretionMHC-IIPotent neutralization
2009
Early 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-2
2007
Renal Hemodynamic, Inflammatory, and Apoptotic Responses to Lipopolysaccharide in HO-1−/− Mice
Tracz M, Juncos J, Grande J, Croatt A, Ackerman A, Rajagopalan G, Knutson K, Badley A, Griffin M, Alam J, Nath K. Renal Hemodynamic, Inflammatory, and Apoptotic Responses to Lipopolysaccharide in HO-1−/− Mice. American Journal Of Pathology 2007, 170: 1820-1830. PMID: 17525251, PMCID: PMC1899452, DOI: 10.2353/ajpath.2007.061093.Peer-Reviewed Original ResearchConceptsHeme oxygenase-1Immune cellsNF-kappaBRenal cytokine expressionRenal hemodynamic responseRenal blood flowGene heme oxygenase-1Glomerular filtration rateHO-1 deficiencyBone marrow progenitorsWidespread apoptosisHO-1 geneRenal hemodynamicsSepsis syndromeSerum cytokinesSerum levelsTh1 cytokinesClinical outcomesTh2 cytokinesCytokine expressionFiltration rateInflammatory responseHemodynamic responseBlunted activationBlood flow
2006
INTRANASAL EXPOSURE TO STAPHYLOCOCCAL ENTEROTOXIN B ELICITS AN ACUTE SYSTEMIC INFLAMMATORY RESPONSE
Rajagopalan G, Sen M, Singh M, Murali N, Nath K, Iijima K, Kita H, Leontovich A, Gopinathan U, Patel R, David C. INTRANASAL EXPOSURE TO STAPHYLOCOCCAL ENTEROTOXIN B ELICITS AN ACUTE SYSTEMIC INFLAMMATORY RESPONSE. Shock 2006, 25: 647-656. PMID: 16721274, DOI: 10.1097/01.shk.0000209565.92445.7d.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, IntranasalAnimalsCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCytokinesEnterotoxinsGene Expression RegulationHLA-DR3 AntigenHumansInflammationLungMiceMice, KnockoutNeutrophil InfiltrationReceptors, Interleukin-2Receptors, Interleukin-4Signal TransductionSystemic Inflammatory Response SyndromeConceptsII transgenic miceHLA class II transgenic miceStaphylococcal enterotoxin BCD8 T cellsTransgenic miceIntranasal exposureIL-12T cellsIFN-gammaEndogenous class II moleculesSystemic inflammatory response syndromeTCR V beta 8Defective IL-12Serum IFN-gammaSystemic immune activationInflammatory response syndromeSystemic cytokine responseBronchoalveolar lavage fluidMononuclear cell infiltrationPoor immune responsePro-inflammatory cytokinesS. aureus colonizationClass II moleculesIL-4 receptorNeutrophil influx
2002
Staphylococcal enterotoxin B‐induced activation and concomitant resistance to cell death in CD28‐deficient HLA‐DQ8 transgenic mice
Rajagopalan G, Smart M, Marietta E, David C. Staphylococcal enterotoxin B‐induced activation and concomitant resistance to cell death in CD28‐deficient HLA‐DQ8 transgenic mice. International Immunology 2002, 14: 801-812. PMID: 12096040, DOI: 10.1093/intimm/dxf047.Peer-Reviewed Original ResearchConceptsT cellsStaphylococcal enterotoxin BHLA-DQ8IFN-gammaTransgenic miceEnterotoxin BBALB/c splenocytesDQ8 transgenic miceSerum IFN-gammaLess IL-2IL-6 productionAbsence of CD28Role of CD28Activation-induced cell deathCertain effector functionsIL-10Lethal shockIL-2IL-4Immune responseEffector functionsConcomitant resistanceCD28Nitric oxideMice