Reciprocal induction of IL-10 and IL-12 from macrophages by low-density lipoprotein and its oxidized forms.
Atherosclerosis is a chronic inflammatory disease. Several lines of evidence indicate that altered or modified lipoproteins contribute to plaque formation and lesion progression in atherogenesis. In this study we examined if lipoproteins and their oxidized forms can exert an immunomodulatory effect, thereby potentially influencing atherogenesis. We demonstrate that LDL, upon binding to its receptor, induces interleukin (IL)-10 production from macrophages and biases naive T cells to become Th2-like. In contrast, oxLDL induces IL-12 from macrophages and accordingly favors differentiation of naive T cells along a Th1 pathway. IL-10 is a potent anti-inflammatory cytokine with a number of potential effects that could dampen inflammation at sites of vascular wall damage, including downregulation of MHC and adhesion molecules and biasing of adaptive immune responses toward the anti-inflammatory, humoral immune-promoting Th2 T cell subset. These studies assign a new immunomodulatory role to LDLs and offer a potential means to upregulate IL-10 production and prevent arterial inflammation.
Varadhachary
A S
AS
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Monestier
M
M
Salgame
P
P
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000096:biosynthesis*; D008077:Lipoproteins, LDL / Q000276:immunology* / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011973:Receptors, LDL / Q000276:immunology; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; D013601:T-Lymphocytes / Q000276:immunology
D008077:Lipoproteins, LDL; C495138:Olr1 protein, mouse; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma