DiC14-amidine confers new anti-inflammatory properties to phospholipids

Cell Mol Life Sci. 2008 Feb;65(4):620-30. doi: 10.1007/s00018-007-7520-1.

Abstract

The inflammatory effect of unmethylated CpG DNA sequences represents a major obstacle to the use of cationic lipids for in vivo gene therapy. Although the mechanism of CpG-induced inflammatory response is rather well understood nowadays, few solutions have been designed to circumvent this effect in gene therapy experiments. Our previous work has shown that a refractory state towards inflammation can be elicited by preinjecting cationic liposomes. Here, we present evidence that diC14-amidine liposomes confer new anti-inflammatory properties to phospholipids from low-density lipoprotein (LDL) and even to synthetic phospholipids for which such an observation has not been reported so far. Whereas oxidation of LDL lipids was a prerequisite for any anti-inflammatory activity, lipid oxidation is no longer required in our experiments, suggesting that cationic lipids transport phospholipids through a different route and affect different pathways. This opens up new possibilities for manipulating inflammatory responses in gene therapy protocols but also in a general manner in immunological experiments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidines / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Apoptosis / drug effects
  • Cytokines / antagonists & inhibitors
  • Cytokines / metabolism
  • Humans
  • Inflammation / genetics
  • Inflammation / physiopathology*
  • Liposomes
  • Phospholipids / pharmacology*

Substances

  • Amidines
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cytokines
  • Liposomes
  • N-t-butyl-n'-tetradecyl-3-tetradecylaminopropionamidine
  • Phospholipids