Oxidized-HDL3 modulates the expression of Cox-2 in human endothelial cells.
Modified high density lipoprotein (HDL) has been suggested to modulate endothelial expression of proinflammatory genes. Since oxidised HDL (Ox-HDL) has been found in atheromatous plaques and receptors for modified HDL are present on endothelial cells, we investigated the effect of Ox-HDL3 on the expression of Cox-1 or Cox-2. Ox-HDL3, increased Cox-2 mRNA and protein expression in endothelial cells while no effect on Cox-1 expression was observed. The intracellular pathways involved in this effect were investigated. The incubation with specific inhibitors of intracellular kinases showed that PI3K is mainly involved in the Ox-HDL3-dependent Cox-2 induction. Transient transfection experiments suggested that the NF-IL6 response element in the proximal promoter (-327 to 59) is involved in Ox-HDL3-mediated Cox-2 expression. These data suggest that Ox-HDL induce Cox-2 expression in endothelial cells through a PI3K/NF-IL6-dependent pathway.
Callegari
Elisa
E
Department of Pharmacological Sciences, University of Milan, Milan, Italy.
Norata
Giuseppe D
GD
Inoue
Hiroyasu
H
Catapano
Alberico L
AL
D002070:Butadienes / Q000494:pharmacology; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D015151:Immunoblotting; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000494:pharmacology*; D053440:Lipoproteins, HDL3; D009025:Morpholines / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D010084:Oxidation-Reduction; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011725:Pyridines / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D002070:Butadienes; D002867:Chromones; D004791:Enzyme Inhibitors; D007093:Imidazoles; D008075:Lipoproteins, HDL; D053440:Lipoproteins, HDL3; D009025:Morpholines; D009570:Nitriles; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011725:Pyridines; C113580:U 0126; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580