Therapeutic potential of HUC-MSC-exos primed with IFN-γ against LPS-induced acute lung injury

Objective(s): Human umbilical cord mesenchymal stem cells (HUC-MSCs) are pluripotent stem cells with anti-inflammatory and immunomodulatory properties used in the treatment of acute lung injury (ALI). However, the treatment of ALI using exosomes derived from HUC-MSCs (HUC-MSC-exos) primed with interferon-gamma (IFN-γ-exos) has not been described. This study investigated the effects of IFN-γ-exos on ALI.Materials and Methods: IFN-γ primed and unprimed HUC-MSC-exos (IFN-γ-exos and CON-exos, respectively) were extracted, identified, and traced. A۵۴۹ cells and mice subjected to lipopolysaccharide (LPS)-induced inflammation were treated with IFN-γ-exos or CON-exos. Viability; interleukin (IL)-۱β, IL-۶, tumor necrosis factor (TNF)-α, and reactive oxygen species (ROS) levels; NF-κB p۶۵, and NLRP۳ expression and histology and lung injury scores were measured in cell, supernatant or lung tissue. Results: Indoleamine ۲,۳-dioxygenase (IDO) mRNA expression was elevated in HUC-MSCs primed with ۵ ng/mL IFN-γ (P<۰.۰۰۱), and IFN-γ-exos and CON-exos were successfully extracted. LPS-induced inflammation resulted in decreased cell viability in A۵۴۹ cells, and increased IL-۱β, IL-۶, TNF-α and ROS levels and NF-κB p۶۵ and NLRP۳ expression in A۵۴۹ cells and mice(P<۰.۰۵ to P<۰.۰۰۱). Treatment with IFN-γ-exos and CON-exos increased cell viability and decreased the concentrations of IL-۱β, and ROS, expression of NF-κB p۶۵ and NLRP۳, and the lung injury score, and these effects were more obvious for IFN-γ-exos(P<۰.۰۵ to P<۰.۰۰۱). Conclusion: IFN-γ-exos reduced oxidative stress and inflammatory responses in LPS-induced A۵۴۹ cells and mice. The result demonstrated the therapeutic potential of IFN-γ-exos in LPS-induced ALI.

Keywords:

Acute lung injury , Exosomes , Mesenchymal stem cells , Interferon gamma , Inflammation