2021
Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation
Xian H, Liu Y, Rundberg Nilsson A, Gatchalian R, Crother T, Tourtellotte W, Zhang Y, Aleman-Muench G, Lewis G, Chen W, Kang S, Luevanos M, Trudler D, Lipton S, Soroosh P, Teijaro J, de la Torre J, Arditi M, Karin M, Sanchez-Lopez E. Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation. Immunity 2021, 54: 1463-1477.e11. PMID: 34115964, PMCID: PMC8189765, DOI: 10.1016/j.immuni.2021.05.004.Peer-Reviewed Original ResearchConceptsAcute respiratory distress syndromeInflammasome activationSARS-CoV-2-induced acute respiratory distress syndromeMyeloid-specific ablationSevere COVID-19Anti-diabetic medicationsAnti-inflammatory effectsRespiratory distress syndromeIL-6 secretionNLRP3 inflammasome activationHigh mortality rateCOVID-19 lungsInhibition of ATPDistress syndromePulmonary inflammationIL-6Inflammatory conditionsMetformin inhibitionMetformin inhibitsARDS severityNF-κBNLRP3 ligandsMortality rateAlveolar macrophagesDNA synthesis
2006
HIV-1 coreceptors CCR5 and CXCR4 both mediate neuronal cell death but CCR5 paradoxically can also contribute to protection
Kaul M, Ma Q, Medders K, Desai M, Lipton S. HIV-1 coreceptors CCR5 and CXCR4 both mediate neuronal cell death but CCR5 paradoxically can also contribute to protection. Cell Death & Differentiation 2006, 14: 296-305. PMID: 16841089, DOI: 10.1038/sj.cdd.4402006.Peer-Reviewed Original ResearchConceptsHuman immunodeficiency virus-1Neuronal cell deathStromal cell-derived factor-1HIV-1 envelope glycoprotein gp120Cell-derived factor-1Cell deathHIV-1 coreceptor CCR5Chemokine receptor CCR5Immunodeficiency virus-1Brain-derived cellsEnvelope glycoprotein gp120Intracellular free Ca2Gp120 neurotoxicityCCR5 ligandsHIV coreceptorsP38 mitogen-activated protein kinaseCCR5 agonistsNeuroprotective pathwaysReceptor CCR5Heterologous desensitizationCoreceptor CCR5CXCR4 agonistCCR5Glial culturesGlycoprotein gp120
2000
Cytokine-Stimulated, But Not HIV-Infected, Human Monocyte-Derived Macrophages Produce Neurotoxic Levels of l-Cysteine
Yeh M, Kaul M, Zheng J, Nottet H, Thylin M, Gendelman H, Lipton S. Cytokine-Stimulated, But Not HIV-Infected, Human Monocyte-Derived Macrophages Produce Neurotoxic Levels of l-Cysteine. The Journal Of Immunology 2000, 164: 4265-4270. PMID: 10754324, DOI: 10.4049/jimmunol.164.8.4265.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedCerebral CortexCysteineCytokinesDose-Response Relationship, ImmunologicHIV Envelope Protein gp120HIV-1HumansImmune SeraInterleukin 1 Receptor Antagonist ProteinInterleukin-1Macrophage ActivationMacrophagesMonocytesNeuronsRatsRats, Sprague-DawleyReceptors, Interleukin-1Receptors, N-Methyl-D-AspartateSialoglycoproteinsSphingosineTumor Necrosis Factor-alphaConceptsHuman monocyte-derived macrophagesNeuronal injuryTNF-alphaHIV-1N-methyl-D-aspartate (NMDA) subtypeUninfected cellsMacrophages/microgliaCultured rat cerebrocortical neuronsVirus-infected macrophagesRelease of neurotoxinsRat cerebrocortical neuronsEnvelope glycoprotein gp120Monocyte-derived macrophagesDose-dependent mannerNeuropathological symptomsIL-1betaGlutamate receptorsCerebrocortical neuronsHIVGlycoprotein gp120Mononuclear phagocytesNeurotoxic levelsGp120Human monocytesCytokine stimulation
1999
Chemokines and activated macrophages in HIV gp120-induced neuronal apoptosis
Kaul M, Lipton S. Chemokines and activated macrophages in HIV gp120-induced neuronal apoptosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96: 8212-8216. PMID: 10393974, PMCID: PMC22214, DOI: 10.1073/pnas.96.14.8212.Peer-Reviewed Original ResearchMeSH KeywordsAIDS Dementia ComplexAnimalsApoptosisCells, CulturedCerebral CortexChemokine CCL4Chemokine CCL5Chemokine CXCL12ChemokinesCytokinesEmbryo, MammalianHIV Envelope Protein gp120HIV-1HumansImmunoglobulin FragmentsMacrophage ActivationMacrophage Inflammatory ProteinsMacrophagesNeurogliaNeuronsOligopeptidesRatsRats, Sprague-DawleyRecombinant ProteinsT-LymphocytesConceptsMacrophages/microgliaNeuronal apoptosisChemokine receptorsSDF-1Brain macrophages/microgliaStromal cell-derived factorRat cerebrocortical culturesBeta-chemokines RANTESCell-derived factorNeurotoxic factorsP38 mitogen-activated protein kinase (MAPK) pathwayProportion of cellsInflammatory proteinP38 mitogen-activated protein kinaseGp120SF2Cerebrocortical culturesReceptor CXCR4MicrogliaHuman neuronsHIV gp120CXCR4 receptorMitogen-activated protein kinase pathwayMitogen-activated protein kinaseNeuronsGp120
1994
HIV-related neuronal injury
Lipton S. HIV-related neuronal injury. Molecular Neurobiology 1994, 8: 181-196. PMID: 7999315, DOI: 10.1007/bf02780669.Peer-Reviewed Original ResearchConceptsArachidonic acidExistence of HIVCalcium channel antagonistsVoltage-dependent Ca2Receptor-operated channelsFuture pharmacological interventionsFinal common pathwayAmyotrophic lateral sclerosisPlatelet-activating factorDysfunction of cognitionDemise of neuronsNeuropathic painAdult patientsAIDS dementiaNeuronal injuryNeurological manifestationsNeuronal damageImmunodeficiency syndromeAIDS patientsChannel antagonistsNMDA antagonistsNeuronal susceptibilityPharmacological interventionsLateral sclerosisParkinson's diseaseUpdate on current models of HIV-related neuronal injury: Platelet-activating factor, arachidonic acid and nitric oxide
Lipton S, Yeh M, Dreyer E. Update on current models of HIV-related neuronal injury: Platelet-activating factor, arachidonic acid and nitric oxide. Advances In Neuroimmunology 1994, 4: 181-188. PMID: 7874385, DOI: 10.1016/s0960-5428(06)80255-x.Peer-Reviewed Original ResearchConceptsMacrophages/microgliaNeuronal injuryPlatelet-activating factorArachidonic acidHuman immunodeficiency virus type 1Nitric oxideHIV-1 envelope protein gp120Immunodeficiency virus type 1N-methyl-D-aspartate agonistExistence of HIVBrains of patientsHalf of childrenEnvelope protein gp120Third of adultsVirus type 1Dysfunction of cognitionDemise of neuronsNeurological manifestationsImmunodeficiency syndromeAIDS patientsProtein gp120Neurotoxic substancesHIVMonocytoid cellsExcessive influx