Song Gyun Jee, Kim Seong-Min, Park Ki-Hoon, Kim Jihoe, Choi Inho, Cho Kyung-Hyun
School of Biotechnology, Yeungnam University, Gyeongsan 712-749, Republic of Korea; Research Institute of Protein Sensor, Yeungnam University, Gyeongsan 712-749, Republic of Korea; BK21Plus Program Serum Biomedical Research and Education Team, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
School of Biotechnology, Yeungnam University, Gyeongsan 712-749, Republic of Korea; Research Institute of Protein Sensor, Yeungnam University, Gyeongsan 712-749, Republic of Korea; BK21Plus Program Serum Biomedical Research and Education Team, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
Biochem Biophys Res Commun. 2015 Jan 30;457(1):112-8. doi: 10.1016/j.bbrc.2014.12.028. Epub 2014 Dec 17.
High density lipoprotein (HDL) receptor, scavenger receptor class B, type I (SR-BI), mediates selective cholesteryl ester uptake from lipoproteins into the liver as well as cholesterol efflux from macrophages to HDL. Recently, strong evidence has demonstrated the anti-inflammatory effect of HDL, although the mechanism of action is not fully understood. In this study, we showed that the anti-inflammatory effects of HDL are dependent on SR-BI expression in THP-1 macrophages. Consistent with earlier findings, pretreatment of macrophages with HDL abolished LPS-induced TNFα production. HDL also inhibited LPS-induced NF-κB activation. In addition, knockdown of SR-BI or inhibition of SR-BI ligand binding abolished the anti-inflammatory effect of HDL. SR-BI is a multi-ligand receptor that binds to modified lipoproteins as well as native HDL. Since modified lipoproteins have pro-inflammatory properties, it is unclear whether SR-BI activated by modified HDL has an anti- or pro-inflammatory effect. Glycated HDL induced NF-κB activation and cytokine production in macrophages in vitro, suggesting a pro-inflammatory effect for modified HDL. Moreover, inhibition of SR-BI function or expression potentiated glycated HDL-induced TNF-α production, suggesting an anti-inflammatory effect for SR-BI. In conclusion, SR-BI plays an important function in regulating HDL-mediated anti-inflammatory response in macrophages.
高密度脂蛋白（HDL）受体，即B类清道夫受体I型（SR-BI），介导脂蛋白中的胆固醇酯选择性摄取进入肝脏以及巨噬细胞中的胆固醇外流至HDL。最近，有力证据表明HDL具有抗炎作用，尽管其作用机制尚未完全明确。在本研究中，我们表明HDL的抗炎作用依赖于THP-1巨噬细胞中SR-BI的表达。与早期研究结果一致，用HDL预处理巨噬细胞可消除脂多糖（LPS）诱导的肿瘤坏死因子α（TNFα）产生。HDL还抑制LPS诱导的核因子κB（NF-κB）激活。此外，敲低SR-BI或抑制SR-BI配体结合可消除HDL的抗炎作用。SR-BI是一种多配体受体，可与修饰的脂蛋白以及天然HDL结合。由于修饰的脂蛋白具有促炎特性，尚不清楚被修饰的HDL激活的SR-BI具有抗炎还是促炎作用。糖化HDL在体外诱导巨噬细胞中的NF-κB激活和细胞因子产生，提示修饰的HDL具有促炎作用。此外，抑制SR-BI功能或表达可增强糖化HDL诱导的TNF-α产生，提示SR-BI具有抗炎作用。总之，SR-BI在调节巨噬细胞中HDL介导的抗炎反应中发挥重要作用。
