title: Changes in gene expression pattern of human primary macrophages induced by carbosilane dendrimer 2G-NN16.
abstract: OBJECTIVE
  The use of dendrimers for biomedical applications has emerged with promising results. 2G-NN16 is a carbosilane dendrimer with sixteen positive charges per molecule tested to be capable to bind and release antisense oligonucleotides (ODNs) and small interference RNA (siRNA) in vitro. In spite of low cytotoxicity observed for these dendrimers, little is known about cellular changes they produce in cells in general and in immune cells in particular.
  
  
  METHODS
  Genomic technologies allow us to identify global gene expression profile changes in macrophages exposed to a non-toxic concentration (5 microM) of 2G-NN16, alone or complexed with a random siRNA (dendriplex). Results were confirmed by quantitative real-time RT-PCR.
  
  
  RESULTS
  Exposing macrophages to this dendrimer or dendriplex causes multiple gene expression changes, but no specific action of random siRNA was detected. Pathway analysis of differentially expressed genes shows the altered functions to be immune response, proliferation and transcription regulation. Interleukin 17F (IL17F) was the most regulated gene.
  
  
  CONCLUSIONS
  Global gene expression profiles are a highly sensitive method to measure the toxicity degree of a gene delivery vehicle. The strong repression of IL17F, IL23R and IL23A, all of which are involved in autoimmune disease, by this particular dendrimer suggests a potential pharmacological application.
authors.affiliation: Laboratory of Pharmacogenetics and Pharmacogenomics, Hospital General Universitario Gregorio Marañon, 28007, Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Gras
authors.forename: Luis
authors.initials: L
authors.lastname: Almonacid
authors.forename: Paula
authors.initials: P
authors.lastname: Ortega
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Serramia
authors.forename: Rafael
authors.initials: R
authors.lastname: Gomez
authors.forename: F Javier
authors.initials: FJ
authors.lastname: de la Mata
authors.forename: Luis A
authors.initials: LA
authors.lastname: Lopez-Fernandez
authors.forename: M Angeles
authors.initials: MA
authors.lastname: Muñoz-Fernandez
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D050091:Dendrimers / Q000737:chemistry / Q000633:toxicity*; D004337:Drug Carriers / Q000737:chemistry / Q000633:toxicity*; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D018014:Gene Transfer Techniques; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D015394:Molecular Structure; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012821:Silanes / Q000737:chemistry / Q000633:toxicity*
chemical_list: D050091:Dendrimers; D004337:Drug Carriers; D012821:Silanes; C504072:carbosilane