Mildly oxidized low-density lipoproteins decrease early production of interleukin 2 and nuclear factor kappaB binding to DNA in activated T-lymphocytes.
Activated T-lymphocytes are found early in atherosclerosis lesions, but little is known about their role. Oxidized low-density lipoproteins (oxLDLs) are considered to be involved in the pathogenesis of the lesions, and we have previously demonstrated that oxLDLs inhibit not only interleukin (IL)-2-receptor expression on the surface of in vitro-activated T-lymphocytes but also their proliferation. We have now investigated the effect of oxLDLs on blast differentiation, on IL-2 synthesis and on the activation of the nuclear factor kappaB (NF-kappaB) system in activated lymphocytes. Mildly oxLDLs (50 and 100 microgram/ml) decreased the number of lymphoblasts and the level of IL-2 concentration in the culture supernatants after activation of lymphocytes by phytohaemagglutinin and PMA+ionomycin. The inhibition of IL-2 production was observed in the CD3(+) T-lymphocyte cytoplasm as early as 4 h after activation by PMA+ionomycin. The study of NF-kappaB showed that oxLDLs led to a decrease of activation-induced p65/p50 NF-kappaB heterodimer binding to DNA, whereas the presence of the constitutive nuclear form of p50 dimer was unchanged. This was correlated with an unchanged level of the active form of the cytosolic inhibitor protein IkappaB-alpha. Taken together, these observations suggest that the immunosuppressive effect of oxLDLs might operate via a dysregulation of the T-lymphocyte activation mechanisms.
Caspar-Bauguil
S
S
INSERM U 466, Institut Louis Bugnard, CHU Rangueil, 31403 Toulouse Cedex 4, France.
Tkaczuk
J
J
Haure
M J
MJ
Durand
M
M
Alcouffe
J
J
Thomsen
M
M
Salvayre
R
R
Benoist
H
H
D001161:Arteriosclerosis / Q000209:etiology; D002454:Cell Differentiation; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007376:Interleukin-2 / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008213:Lymphocyte Activation; D016328:NF-kappa B / Q000378:metabolism*; D010084:Oxidation-Reduction; D011485:Protein Binding; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*
D007376:Interleukin-2; D008077:Lipoproteins, LDL; D016328:NF-kappa B; C099252:oxidized low density lipoprotein; D004247:DNA