Departments of Microbiology & Immunology, University of Louisville, Louisville, KY 40202, USA.
Am J Reprod Immunol. 2011 Jan;65(1):65-77. doi: 10.1111/j.1600-0897.2010.00880.x.
trophoblast cells have been demonstrated to regulate monocyte migration and differentiation, leading to pro-inflammatory profiles. Because trophoblast cells release exosomes with immunoregulatory properties, trophoblast-derived exosomes are proposed to 'educate' monocytes, creating a pro-inflammatory environment.
exosomes were isolated from conditioned media of Swan71 cells by ultrafiltration and ultracentrifugation. Exosome-induced migration was assessed using a two-chamber system. Cytokine profiles were defined using cytokine arrays, and mRNA levels of affected cytokines were examined by qRT-PCR and ELISA.
within 20 min, 8-10% of monocytes took up labeled exosomes isolated from Swan71 cells. Trophoblast-derived exosomes increased monocyte migration in a dose-dependent manner and produced significant increases in production of interleukin (IL)-1β, IL-6, Serpin-E1, granulocyte colony-stimulating factor, granulocyte/monocyte colony-stimulating factor, and tumor necrosis factor-α.
this study presents the initial demonstration that trophoblast-derived exosomes are capable of recruiting and 'educating' monocytes to produce pro-inflammatory cytokine/chemokine profiles in a cell-contact-independent manner.
已证实滋养层细胞可调节单核细胞的迁移和分化,导致促炎表型。由于滋养层细胞释放具有免疫调节特性的外泌体,因此推测滋养层衍生的外泌体可以“教育”单核细胞,从而创造促炎环境。
通过超滤和超速离心从 Swan71 细胞的条件培养基中分离出外泌体。使用双室系统评估外泌体诱导的迁移。使用细胞因子阵列定义细胞因子谱,并通过 qRT-PCR 和 ELISA 检查受影响细胞因子的 mRNA 水平。
在 20 分钟内,8-10%的单核细胞摄取了从 Swan71 细胞中分离的标记外泌体。滋养层衍生的外泌体以剂量依赖性方式增加单核细胞的迁移,并显著增加白细胞介素 (IL)-1β、IL-6、Serpin-E1、粒细胞集落刺激因子、粒细胞/单核细胞集落刺激因子和肿瘤坏死因子-α的产生。
本研究首次证明滋养层衍生的外泌体能够招募和“教育”单核细胞,以非细胞接触依赖的方式产生促炎细胞因子/趋化因子谱。