© 2000 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Oxidized LDL–Induced NF-
B Activation and Subsequent Expression of Proinflammatory Genes Are Defective in Monocyte-Derived Macrophages From CD36-Deficient Patients
From the Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan.
Correspondence to Shizuya Yamashita, MD, PhD, Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2–2 Yamadaoka, Suita, Osaka 565-0871 Japan. E-mail shizu{at}imed2.med.osaka-u.ac.jp
Abstract—CD36 is 1 of the class B
scavenger receptor expressed on monocytes, monocyte-derived
macrophages (M
), platelets, and adipocytes. In our
previous studies, we reported that the uptake of oxidized low density
lipoproteins (OxLDLs) is reduced by 
50% in M from CD36-deficient
patients compared with that in control subjects. Recently, we have
shown that CD36 is highly expressed in human atherosclerotic aorta.
Possibilities have been raised that besides the wide distribution and
multifunctional characteristics of CD36, this molecule may also be
involved in the mediation of intracellular signaling. The aim of the
present study was to elucidate the role of CD36 in cytokine
secretion and to investigate the CD36-mediated intracellular signaling
stimulated by OxLDL. On addition of OxLDL or thrombospondin-1,
the M from CD36-deficient patients secreted significantly less
amounts of tumor necrosis factor-
(TNF-) and interleukin-1ß
(IL-1ß) compared with those from controls. RNase protection assay
with multiprobe template sets demonstrated that after incubation with
OxLDL, the mRNAs of a variety of cytokines, including genes
encoding IL-1Ra, IL-1ß, IL-6, TNF- and -ß, and interferon
(IFN)-
and -ß, were significantly lower in the M of patients.
The addition of antibody against CD36 attenuated this OxLDL-induced
response in controls. We also observed a reduced response in nuclear
factor-
B (NF-B) activity in OxLDL-stimulated M from
CD36-deficient patients. Unlike OxLDL, stimulation by
lipopolysaccharide induced an increase in NF-B activity in
M from CD36-deficient patients, suggesting that
lipopolysaccharide-mediated signaling was conserved. These
results demonstrate that in addition to the reduced OxLDL uptake that
we reported previously, CD36-deficient patients may also have an
impaired response of OxLDL-induced NF-B activation and subsequent
cytokine expression.
Key Words: atherosclerosis • CD36 • monocyte-derived macrophages • oxidized LDL • cytokines
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