Apoptotic mimicry: phosphatidylserine liposomes reduce inflammation through activation of peroxisome proliferator-activated receptors (PPARs) in vivo.
OBJECTIVE
Recently, there has been much attention paid to understanding the molecular mechanisms underlying apoptosis and the functional consequences of apoptotic body clearance by phagocytes. In an attempt to investigate this latter aspect, the present study evaluated the anti-inflammatory effects of in vivo administration of phosphatidylserine (PS) liposomes, a well-characterised membrane component expressed during apoptosis. The participation of peroxisome proliferator-activated receptors (PPARs) in PS-mediated effects was also investigated.


METHODS
The anti-inflammatory effect of PS liposomes on the delayed phase of carrageenan mouse paw oedema was studied. PS liposomes were injected at different doses and times, after carrageenan. Hind paws were collected for evaluation of interleukin-1beta (IL-1beta) levels, myeloperoxidase (MPO) and N-acetyl-glucosaminidase (NAG) activities and Evans blue dye leakage. Participation of PPAR pathways was explored by using PPAR antagonists (BADGE and GW9662).


RESULTS
Administration of PS, but not phosphatidylcholine (PC), liposomes (20-200 mg kg(-1), i.p., 8 h after carrageenan) reduced the paw oedema in a dose-dependent manner. PS liposomes were effective even when administered 24 and 48 h after carrageenan, a time at which indomethacin (1 mg kg(-1), i.p.) had no significant effects. Carrageenan-induced Evans blue leakage and IL-1beta production was decreased in PS-treated paws. The PPAR antagonists (BADGE and GW9662) partially prevented the anti-inflammatory effects of PS administration.


CONCLUSIONS
PS liposomes have anti-inflammatory effects in vivo that are at least partly dependent on PPAR activation. Therapeutic strategies mimicking apoptosis may be useful for the treatment of inflammatory disorders.
Ramos
G C
GC
Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Fernandes
D
D
Charão
C T
CT
Souza
D G
DG
Teixeira
M M
MM
Assreuy
J
J
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002351:Carrageenan; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy*; D008081:Liposomes; D051379:Mice; D047492:Peroxisome Proliferator-Activated Receptors / Q000187:drug effects* / Q000378:metabolism; D010713:Phosphatidylcholines / Q000494:pharmacology; D010718:Phosphatidylserines / Q000008:administration & dosage / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D008081:Liposomes; D047492:Peroxisome Proliferator-Activated Receptors; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D002351:Carrageenan; D007213:Indomethacin