DiC14-amidine confers new anti-inflammatory properties to phospholipids.
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.
Lonez
C
C
Center of Structural Biology and Bioinformatics, Laboratory of Structure and Function of Biological Membranes, Université Libre de Bruxelles, Campus Plaine CP 206/2, 1050, Brussels, Belgium.
Legat
A
A
Vandenbranden
M
M
Ruysschaert
J-M
JM
D000578:Amidines / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000503:physiopathology*; D008081:Liposomes; D010743:Phospholipids / Q000494:pharmacology*
D000578:Amidines; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D008081:Liposomes; C089665:N-t-butyl-n'-tetradecyl-3-tetradecylaminopropionamidine; D010743:Phospholipids