Ferrero-Andrés Ana, Closa Daniel, Roselló-Catafau Joan, Folch-Puy Emma
Experimental Pathology Department, Institut d'Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones Científicas (IIBB-CSIC), 08036 Barcelona, Spain.
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain.
Polymers (Basel). 2020 Dec 18;12(12):3044. doi: 10.3390/polym12123044.
Polyethylene glycols (PEGs) are neutral polymers widely used in biomedical applications due to its hydrophilicity and biocompatibility. Exosomes are small vesicles secreted by nearly all cell types and play an important role in normal and pathological conditions. The purpose of this study was to evaluate the role of a 35-kDa molecular weight PEG (PEG35) on the modulation of exosome-mediated inflammation. Human macrophage-like cells THP-1, epithelial BICR-18, and CAPAN-2 cells were exposed to PEG35 prior to incubation with exosomes of different cellular origins. Exosome internalization was evaluated by confocal microscopy and flow cytometry. In another set of experiments, macrophages were treated with increasing concentrations of PEG35 prior to exposure with the appropriate stimuli: lipopolysaccharide, BICR-18-derived exosomes, or exosomes from acute pancreatitis-induced rats. Nuclear Factor Kappa B (NFκB) and Signal transducer and activator of transcription 3 (STAT3) activation and the expression levels of pro-inflammatory Interleukin 1β (IL1β) were determined. PEG35 administration significantly enhanced the internalization of exosomes in both macrophages and epithelial cells. Further, PEG35 ameliorated the inflammatory response induced by acute pancreatitis-derived exosomes by reducing the expression of IL1β and p65 nuclear translocation. Our results revealed that PEG35 promotes the cellular uptake of exosomes and modulates the pro-inflammatory effect of acute pancreatitis-derived vesicles through inhibition of NFκB, thus emphasizing the potential value of PEG35 as an anti-inflammatory agent for biomedical purposes.
聚乙二醇（PEGs）是中性聚合物，因其亲水性和生物相容性而广泛应用于生物医学领域。外泌体是几乎所有细胞类型分泌的小囊泡，在正常和病理条件下发挥重要作用。本研究的目的是评估分子量为35 kDa的聚乙二醇（PEG35）对外泌体介导的炎症调节作用。在与不同细胞来源的外泌体孵育之前，将人巨噬细胞样细胞THP-1、上皮细胞BICR-18和CAPAN-2细胞暴露于PEG35。通过共聚焦显微镜和流式细胞术评估外泌体的内化。在另一组实验中，在用适当的刺激物（脂多糖、BICR-18来源的外泌体或急性胰腺炎诱导大鼠的外泌体）刺激巨噬细胞之前，先用递增浓度的PEG35处理巨噬细胞。测定核因子κB（NFκB）和信号转导及转录激活因子3（STAT3）的激活情况以及促炎白细胞介素1β（IL1β）的表达水平。PEG35的给药显著增强了巨噬细胞和上皮细胞中外泌体的内化。此外，PEG35通过降低IL1β的表达和p65核转位，改善了急性胰腺炎来源的外泌体诱导的炎症反应。我们的结果表明，PEG35促进外泌体的细胞摄取，并通过抑制NFκB调节急性胰腺炎来源囊泡的促炎作用，从而强调了PEG35作为生物医学用途抗炎剂的潜在价值。
