Electronegative LDL induces Fas and modifies gene expression in mononuclear cells.
Electronegative LDL (LDL(-)) is a minor modified LDL subfraction that promotes cytokine release by human mononuclear cells. The aim of the current study was to evaluate changes in gene expression induced by LDL(-) versus native LDL in lymphocytes and monocytes. Therefore, mononuclear cells were incubated with these LDL subfractions and their effects on expression in human whole genome were analyzed by gene array. Differential expression of the genes was quantified by real-time RT-PCR. LDL(-) altered the gene expression pattern, particularly of inflammatory genes. LDL(-) down-regulated CD36 and colony-stimulating factor 1 receptor (CSF1R) genes and up-regulated Fas expression and Fas protein on cellular membrane. LDL(-) seemed to promote the alterations in these genes by activation of NF-kB and inhibition of AP1 and PPARG. In conclusion, LDL(-) induced changes in gene expression in monocytes and lymphocytes. Fas up-regulation suggests a proinflammatory action; however, CSF1R and CD36 down-regulation could decrease monocyte differentiation and activation. Therefore, LDL(-) promoted not only inflammatory effects but also counteracting actions in circulating mononuclear cells.
Bancells
Cristina
C
Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Sanchez-Quesada
Jose Luis
JL
Birkelund
Ragnhild
R
Ordonez-Llanos
Jordi
J
Benitez
Sonia
S
D018955:CD36 Antigens / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000097:blood / Q000494:pharmacology*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D019014:fas Receptor / Q000378:metabolism*
D018955:CD36 Antigens; C491901:FAS protein, human; D008077:Lipoproteins, LDL; D019014:fas Receptor; D016186:Receptor, Macrophage Colony-Stimulating Factor