Transactions of the American Clinical and Climatological Association · 2019
TARGETING TARGETED TREATMENT FOR IMMUNE AND NON-IMMUNE KIDNEY DISEASES.
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Tsokos George C, Tsokos Maria G
Аннотация
We have found that calcium calmodulin kinase IV is increased in T cells, podocytes, and mesangial cells from patients with systemic lupus erythematosus, as well as in lupus-prone mice, podocytes of patients with focal segmental glomerulosclerosis, and in mice injected with doxorubicin. We showed that this accounts for aberrant T cell function and glomerular damage. Using nanoparticles (nlg) loaded with a small drug inhibitor of calcium calmodulin kinase IV and tagged with antibodies directed to CD4 we have been able to show inhibition of autoimmunity and lupus nephritis. Also, using nlg tagged with antibodies to nephrin, we showed suppression of nephritis in lupus-prone mice and of glomerular damage in mice exposed to doxorubicin. We propose the development of approaches to deliver drugs to cells in a targeted and precise manner.
Предметные рубрики MeSH
AnimalsAntibiotics, AntineoplasticBenzylaminesCD4 AntigensCalcium-Calmodulin-Dependent Protein Kinase Type 4DNA MethylationDisease Models, AnimalDoxorubicinDrug Delivery SystemsGlomerulosclerosis, Focal SegmentalHumansLupus Erythematosus, SystemicLupus NephritisMembrane ProteinsMiceMice, Inbred MRL lprMolecular Targeted TherapyNanoparticlesProtein Kinase InhibitorsSulfonamidesT-LymphocytesT-Lymphocytes, RegulatoryTh17 CellsBenzenesulfonamides