Lipoxin A4 inhibits acute edema in mice: implications for the anti-edematogenic mechanism induced by aspirin.
Lipoxin A4 (LXA4) is a lipid mediator that plays an important role in the resolution of inflammation. However, the role of LXA4 and aspirin (ASA)-triggered lipoxins (ATLs) in inflammatory edema formation remains unclear. Here, we investigated the inhibitory role played by LXA4 in the carrageenan-induced and other inflammatory mediator-induced edematogenic response in mice, and also assessed the role of ATLs in the anti-edematogenic action of aspirin. Our results showed that LXA4 (1-20 ng/paw or 5 microg/kg i.p.) was effective in inhibiting carrageenan-induced paw edema from 30 min to 2 h. LXA4 (10 ng/paw) was also able to acutely inhibit PAF-, histamine-, PGE2- or bradykinin-induced paw edema, as well as the PAF-induced myeloperoxidase activity increase in the paws. Likewise, LXA4 (10 ng/cavity) also inhibited the pleural edema triggered by histamine (1h), and this response was not followed by leukocyte accumulation. Of note, the lipoxin receptor (ALX-r) antagonist Boc2 (butoxycarbonyl-Phe-Leu-Phe-Leu-Phe, 200 ng/paw) significantly reverted the anti-edematogenic effect of ASA (300 mg/kg p.o.) against carrageenan, PAF, PGE2 and BK, without affecting the anti-edematogenic action caused by indomethacin (3 mg/kg i.p.) in the carrageenan-induced paw edema. Collectively, our results demonstrate for the first time that LXA4 displays an acute and rapid onset anti-edematogenic activity that does not discriminate among different pro-inflammatory stimuli, an effect that is most likely independent of its action on the leukocyte influx. Finally, the present study demonstrates that ATLs exert a very important role in the acute anti-edematogenic action of ASA.
Menezes-de-Lima
Octavio
O
Department of Pharmacology, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, Brazil.
Kassuya
Cândida A L
CA
Nascimento
Andrey F Z
AF
Henriques
Maria das Graças M O
Md
Calixto
João B
JB
D000208:Acute Disease; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology; D002351:Carrageenan; D015232:Dinoprostone / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D005528:Foot / Q000473:pathology; D006614:Hindlimb / Q000187:drug effects / Q000473:pathology; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology; D044045:Lipoxins / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000008:administration & dosage / Q000494:pharmacology; D010998:Pleurisy / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D044067:Receptors, Lipoxin / Q000037:antagonists & inhibitors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D044045:Lipoxins; D009842:Oligopeptides; D010972:Platelet Activating Factor; D044067:Receptors, Lipoxin; C040527:lipoxin A4; C033373:butyloxycarbonyl-phenylalanyl-leucyl-phenylalanyl-leucyl-phenylalanine; D006632:Histamine; D002351:Carrageenan; D015232:Dinoprostone; D001241:Aspirin; D001920:Bradykinin; D007213:Indomethacin