Quan Hongxuan, Park Hee Chul, Kim Yongjoon, Yang Hyeong-Cheol
Department of Dental Biomaterials Science and Dental Research Institute, School of Dentistry, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.
J Biomed Mater Res A. 2017 May;105(5):1479-1486. doi: 10.1002/jbm.a.35981. Epub 2017 Mar 20.
Inhibiting liposome uptake by macrophages using polyethylene glycol (PEG) surface modifications is a widely used approach for extending the half-life of liposomes circulating in the blood. However, the biological effects of PEGylated liposomes on macrophages have not yet been thoroughly investigated. The purpose of this study was to examine the effects of PEGylated phosphatidylserine-containing liposomes (PEG-PSLs) on the expression of two inflammation-associated cytokines, tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β), in the murine macrophage-like cell line RAW 264.7. Previous studies have demonstrated that PSLs inhibit TNF-α secretion and enhance TGF-β synthesis in macrophages by mimicking apoptotic cells. We found that PEGylation differentially affected the TNF-α and TGF-β levels. The PSL-mediated inhibitory effect on TNF-α secretion was enhanced by PEGylation, and PEG-PSLs decreased TGF-β levels compared with non-PEGylated PSLs. Fluorescence-activated cell sorting analysis demonstrated that 1% PEGylation disturbed the incorporation of PSLs into macrophages. The interference of uptake is thought to extend the binding interaction between PS to PS receptors for PSL-mediated inhibition of TNF-α expression. Together, these findings indicate that PEG-PSLs can prevent TNF-α secretion without increasing TGF-β levels in macrophages, and they support the potential clinical use of PEG-PSLs as anti-inflammatory agents with a relatively low potential to induce tissue fibrosis. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1479-1486, 2017.
使用聚乙二醇（PEG）表面修饰来抑制巨噬细胞对脂质体的摄取是一种广泛应用的方法，用于延长血液中循环脂质体的半衰期。然而，聚乙二醇化脂质体对巨噬细胞的生物学效应尚未得到充分研究。本研究的目的是检测聚乙二醇化含磷脂酰丝氨酸脂质体（PEG-PSLs）对小鼠巨噬细胞样细胞系RAW 264.7中两种炎症相关细胞因子肿瘤坏死因子-α（TNF-α）和转化生长因子-β（TGF-β）表达的影响。先前的研究表明，PSLs通过模拟凋亡细胞来抑制巨噬细胞中TNF-α的分泌并增强TGF-β的合成。我们发现聚乙二醇化对TNF-α和TGF-β水平有不同的影响。聚乙二醇化增强了PSL对TNF-α分泌的抑制作用，并且与未聚乙二醇化的PSLs相比，PEG-PSLs降低了TGF-β水平。荧光激活细胞分选分析表明，1%的聚乙二醇化干扰了PSLs进入巨噬细胞。摄取的干扰被认为会延长PS与PS受体之间的结合相互作用，从而实现PSL介导的对TNF-α表达的抑制。总之，这些发现表明PEG-PSLs可以在不增加巨噬细胞中TGF-β水平的情况下预防TNF-α分泌，并且支持PEG-PSLs作为具有相对较低诱导组织纤维化潜力的抗炎剂的潜在临床应用。© 2017威利期刊公司。《生物医学材料研究杂志》A部分：105A：1479 - 1486，2017年。
