title: The inhibition of Th17 immune response in vitro and in vivo by the carbosilane dendrimer 2G-NN16.
abstract: We evaluated the 2G-NN16-carbosilane dendrimer activities in Th17 response as a potential therapy for Th17 deregulated pathologies. IL17A, IL17F, IL22, IL23 and other interleukins secreted by Th17 cells CD4+ cells were down regulated when cells were cultured in the presence of this dendrimer. Furthermore, IL17F and IL17A protein levels in splenocytes from mice pretreated with 2G-NN16 dendrimer in a Th17 induction mouse model were lower than those corresponding to PBS treated mice. Treatment of mice with 2G-NN16 inhibited the Th17 response causing much more pathogenicity as indicated by the increase in the number of Candida albicans colonies in the kidneys as compared to PBS-treated mice. All these results suggest a potential pharmacological application for this dendrimer in the therapy of Th17-mediated diseases.
authors.affiliation: Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Doctor Esquerdo 46, 28007-Madrid, Spain. rgras.hgugm@salud.madrid.org
authors.forename: Rafael
authors.initials: R
authors.lastname: Gras
authors.forename: Miguel
authors.initials: M
authors.lastname: Relloso
authors.forename: María I
authors.initials: MI
authors.lastname: García
authors.forename: F Javier
authors.initials: FJ
authors.lastname: de la Mata
authors.forename: Rafael
authors.initials: R
authors.lastname: Gómez
authors.forename: Luis A
authors.initials: LA
authors.lastname: López-Fernández
authors.forename: M Angeles
authors.initials: MA
authors.lastname: Muñoz-Fernández
mesh_terms: D000818:Animals; D002176:Candida albicans / Q000187:drug effects / Q000276:immunology; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000494:pharmacology* / Q000633:toxicity; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D054399:Receptors, CCR6 / Q000378:metabolism; D012821:Silanes / Q000494:pharmacology* / Q000633:toxicity; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
chemical_list: C572050:2G-NN16; C106311:CCR6 protein, human; D050091:Dendrimers; D020381:Interleukin-17; D054399:Receptors, CCR6; D012821:Silanes; C504072:carbosilane