Role of PPAR-gamma in the modulation of CD36 and FcgammaRII induced by LDL with low and high degrees of oxidation during the differentiation of the monocytic THP-1 cell line.
Scavenger or Fcgamma receptors are important for capture and clearance of modified LDL particles by monocytes/macrophages. Uptake via scavenger receptors is not regulated by intracellular levels of cholesterol and in consequence, macrophages develop into foam cells in the arterial intima. The levels of scavenger receptor CD36 are increased in atherosclerotic lesions and there is evidence that some components of oxLDL auto-regulate the expression of this receptor. Fcgamma receptor expression is increased in cardiovascular diseases but it is not known weather their expression is regulated by oxLDL. The biological properties of oxLDLs vary depending on the degree of oxidation. In the present study we investigated the effect of LDL particles showing extensive or low oxidation (HoxLDL and LoxLDL) on the expression of CD36 and FcgammaRII in a human monocytic cell line (THP-1), differentiated or not to macrophage, and the involvement of PPARgamma. It was found that both forms of oxLDL are able to increase the expression of CD36 and FcgammaRII and that this effect is dependent on the degree of oxidation and of the stage of cell differentiation (monocyte or macrophage). We also showed that the increased expression of FcgammaRII is dependent on PPARgamma whereas that of the CD36 is independent of PPARgamma.
Rios
Francisco J O
FJ
Laboratórios de Imunofisiopatologia e Imunofarmacologia, Instituto de Ciencias Biomédicas, Universidade de Sao Paulo, Brazil.
Jancar
Sonia
S
Melo
Ivo B
IB
Ketelhuth
Daniel F J
DF
Gidlund
Magnus
M
D000813:Anilides / Q000494:pharmacology; D039481:CD11b Antigen / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D018955:CD36 Antigens / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002852:Chromatography, Ion Exchange; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects*; D010084:Oxidation-Reduction / Q000187:drug effects; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism*; D000077154:Rosiglitazone; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D039481:CD11b Antigen; D018821:CD18 Antigens; D018955:CD36 Antigens; D005231:Fatty Acids, Unsaturated; C080568:Fc gamma receptor IIA; C509295:ITGAM protein, human; D008077:Lipoproteins, LDL; D047495:PPAR gamma; D017452:Receptors, IgG; D045162:Thiazolidinediones; D017392:Thiobarbituric Acid Reactive Substances; C099252:oxidized low density lipoprotein; D000077154:Rosiglitazone; D013755:Tetradecanoylphorbol Acetate