Anti-obesity and anti-inflammatory effects of macrophage-targeted interleukin-10-conjugated liposomes in obese mice
Anti-obesity and anti-inflammatory effects of macrophage-targeted interleukin-10-conjugated liposomes in obese mice
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DOI：
10.1016/j.biomaterials.2016.09.018
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发表时间：
2016-12-01
期刊：
影响因子：
14
通讯作者：
Kang, Jeong-Hun
中科院分区：
文献类型：
--
作者：
Toita, Riki;Kawano, Takahito;Kang, Jeong-Hun
肥胖与慢性炎症有关，是包括慢性肾脏疾病、糖尿病和心血管疾病在内的几种疾病的主要危险因素。巨噬细胞在肥胖引起的炎症发展中起着关键作用。有效地向巨噬细胞输送治疗性抗炎分子，如白介素10，可以显著提高肥胖治疗的疗效。我们使用含有‘Eat-me’信号的磷脂酰丝氨酸(PS)的脂质体(PS包含脂质体；PSL)作为将IL-10运送到巨噬细胞的生物材料载体。IL-10偶联的PSL(PSL-IL10)对巨噬细胞具有较高的亲和力。在肥胖小鼠中，PSL-IL10治疗具有显著的抗肥胖和抗炎作用，如降低血清总胆固醇、脂肪细胞大小、冠状结构、脂肪组织中促炎症细胞因子(IL-6和肿瘤坏死因子α)的分泌、肝损伤、肝脏脂肪变性和炎症灶，而单独使用IL-10或PSL治疗没有明显作用。这些结果表明，由于IL-10和PSL的协同抗炎作用，PSL-IL10具有巨噬细胞靶向能力和增强的抗炎作用，可以作为一种巨噬细胞靶向治疗包括肥胖在内的炎症相关疾病的材料。(C)2016爱思唯尔有限公司。保留所有权利。
Obesity is associated with chronic inflammation and is known as a major risk factor for several diseases including chronic kidney disease, diabetes, and cardiovascular diseases. Macrophages play a critical role in the development of obesity-induced inflammation. Efficient delivery of therapeutic anti-inflammatory molecules, such as interleukin (IL)-10, to macrophages can dramatically improve therapeutic efficacy of obesity treatments. We used liposomes containing the 'eat-me' signal phosphatidylserine (PS) (PS containing liposomes; PSL), which have macrophage targeting ability and anti-inflammatory functions, as a biomaterial carrier for the delivery of IL-10 to macrophages. The IL-10-conjugated PSL (PSL-IL10) showed high affinity for macrophages. In obese mice, PSL-IL10 treatment exhibited significant anti obesity and anti-inflammatory effects, such as reduced serum total cholesterol, adipocyte size, crown like structures, proinflammatory cytokine secretion (IL-6 and tumor necrosis factor a) in adipose tissue, liver injury, hepatic steatosis, and inflammation foci, while treatment with IL-10 or PSL alone did not. These findings suggest that the PSL-IL10 has macrophage targeting ability and enhanced anti-inflammatory effect due to the synergistic anti-inflammatory effects of IL-10 and PSL, and can be used as a macrophage-targeted therapeutic material for inflammation-related diseases, including obesity. (C) 2016 Elsevier Ltd. All rights reserved.