The peroxisome proliferator-activated receptor alpha (PPARalpha) ligand WY 14,643 does not interfere with leukotriene B4 induced adhesion of neutrophils to endothelial cells.
Peroxisome proliferator-activated receptors (PPAR) control discrete genes involved in fatty acid and lipid metabolism. Recently, it was suggested that activation of the alpha isoform of PPAR by the potent proinflammatory mediator leukotriene B4 (LTB4) enhanced degradation of this eicosanoid, offersuggesting a new aspect of down-regulation of inflammation. Here, we studied whether PPARalpha activation (by means of the selective agonist WY 14,643) of endothelial cells, pivotal in the regulation of inflammatory responses, interfered with LTB4 induced adhesion of PMN neutrophil granulocytes in vitro. When endothelial cells were treated with WY 14,643 prior to activation with LTB4 (or fMLP, IL-1beta or TNFalpha, as controls) we could not document any effect on the number of adhering PMN or duration of the response. Thus, this study provides no evidence indicating a regulatory function of PPARalpha in LTB4 induced adhesive interactions between endothelial cells and neutrophils.
Department of Rheumatology, The Karolinska Institute at Huddinge University Hospital, Huddinge, Sweden.
M
M
Heimbürger
J
J
Palmblad
D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D007975:Leukotriene B4 / Q000494:pharmacology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D011743:Pyrimidines / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D014471:Umbilical Veins
D011743:Pyrimidines; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine; C006253:pirinixic acid