Janabi M, Yamashita S, Hirano K, Sakai N, Hiraoka H, Matsumoto K, Zhang Z, Nozaki S, Matsuzawa Y
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Osaka, Japan.
Arterioscler Thromb Vasc Biol. 2000 Aug;20(8):1953-60. doi: 10.1161/01.atv.20.8.1953.
-CD36 is 1 of the class B scavenger receptor expressed on monocytes, monocyte-derived macrophages (Mphi), platelets, and adipocytes. In our previous studies, we reported that the uptake of oxidized low density lipoproteins (OxLDLs) is reduced by approximately 50% in Mphi 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 Mphi from CD36-deficient patients secreted significantly less amounts of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) 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-1beta, IL-6, TNF-alpha and -beta, and interferon (IFN)-gamma and -beta, were significantly lower in the Mphi of patients. The addition of antibody against CD36 attenuated this OxLDL-induced response in controls. We also observed a reduced response in nuclear factor-kappa B (NF-kappa B) activity in OxLDL-stimulated Mphi from CD36-deficient patients. Unlike OxLDL, stimulation by lipopolysaccharide induced an increase in NF-kappa B activity in Mphi 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-kappa B activation and subsequent cytokine expression.
-CD36是B类清道夫受体之一，在单核细胞、单核细胞衍生的巨噬细胞（Mphi）、血小板和脂肪细胞上表达。在我们之前的研究中，我们报道与对照受试者相比，CD36缺陷患者的Mphi对氧化型低密度脂蛋白（OxLDL）的摄取减少了约50%。最近，我们发现CD36在人类动脉粥样硬化主动脉中高度表达。除了CD36广泛的分布和多功能特性外，还提出了该分子可能参与细胞内信号传导介导的可能性。本研究的目的是阐明CD36在细胞因子分泌中的作用，并研究OxLDL刺激的CD36介导的细胞内信号传导。添加OxLDL或血小板反应蛋白-1后，与对照组相比，CD36缺陷患者的Mphi分泌的肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）量显著减少。使用多探针模板集的核糖核酸酶保护试验表明，与OxLDL孵育后，包括编码IL-1Ra、IL-1β、IL-6、TNF-α和-β以及干扰素（IFN）-γ和-β的基因在内的多种细胞因子的mRNA在患者的Mphi中显著降低。添加抗CD36抗体减弱了对照组中这种OxLDL诱导的反应。我们还观察到，CD36缺陷患者的OxLDL刺激的Mphi中核因子-κB（NF-κB）活性的反应降低。与OxLDL不同，脂多糖刺激导致CD36缺陷患者的Mphi中NF-κB活性增加，这表明脂多糖介导的信号传导是保守的。这些结果表明，除了我们之前报道的OxLDL摄取减少外，CD36缺陷患者对OxLDL诱导的NF-κB激活和随后的细胞因子表达的反应也可能受损。
