Carbosilane dendrimer 2G-NN16 represses Tc17 differentiation in primary T CD8+ lymphocytes

Mol Pharm. 2012 Jan 1;9(1):102-10. doi: 10.1021/mp200305u. Epub 2011 Nov 16.

Abstract

We studied changes in gene expression induced by the carbosilane dendrimer 2G-NN16 to evaluate their potential as a vehicle for gene therapy and as medication. Global gene expression profiles on CD8+ T lymphocytes reveal that ribosomal proteins are induced in the presence of 2G-NN16. IL17A and IL17F, the principal interleukins secreted by Tc17 cells, a subset of CD8+ T lymphocytes, were down-regulated when cultured in the presence of this dendrimer. Microarray results were confirmed by real time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). 2G-NN16 also showed a high potential for in vitro inhibition of Tc17 differentiation of CD8+ T lymphocytes in the presence of the Tc17 differentiation molecules IL6 and TGF-B1. These findings suggest that 2G-NN16 could facilitate drug delivery and may be used to treat inflammatory processes driven by Tc17 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / drug effects*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / drug effects*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Dendrimers / adverse effects
  • Dendrimers / chemistry
  • Dendrimers / pharmacology*
  • Down-Regulation / drug effects*
  • Gene Expression Profiling
  • Gene Transfer Techniques / adverse effects
  • Humans
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism
  • Nanoparticles / adverse effects
  • Nanoparticles / chemistry
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / metabolism
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism
  • Silanes / adverse effects
  • Silanes / chemistry
  • Silanes / pharmacology*
  • Up-Regulation / drug effects

Substances

  • 2G-NN16
  • Anti-Inflammatory Agents, Non-Steroidal
  • Dendrimers
  • IL17A protein, human
  • IL17F protein, human
  • Interleukin-17
  • RNA, Messenger
  • Ribosomal Proteins
  • Silanes
  • carbosilane