Polyethylene Glycol 35 (PEG35) Modulates Exosomal Uptake and Function

Abstract

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.

Keywords

• polyethylene glycol
• exosomes
• pancreatitis
• inflammation
• macrophages
• cytokines