No abstract

Lipoxin A 4 (LXA 4 ), as an endogenously produced lipid mediator, promotes the resolution of inflammation. Previously, we demonstrated that LXA 4 stimulated alveolar fluid clearance through alveolar epithelial sodium channel gamma (ENaC-γ). In this study, we sought to investigate the mechanisms of LXA 4 in modulation of ENaC-γ in lipopolysaccharide (LPS)-induced inflammatory lung injury. miR-21 was upregulated during an LPS challenge and downregulated by LXA 4 administration in vivo and in vitro. Serum miR-21 concentration was also elevated in acute respiratory distress syndrome patients as compared with healthy volunteers. LPS increased miR-21 expression by activation of activator protein 1 (AP-1). In A549 cells, miR-21 upregulated phosphorylation of AKT activation via inhibition of phosphatase and tensin homolog (PTEN), and therefore reduced the expression of ENaC-γ. In contrast, LXA 4 reversed LPS-inhibited ENaC-γ expression through inhibition of AP-1 and activation of PTEN. In addition, an miR-21 inhibitor mimicked the effects of LXA 4 ; overexpression of miR-21 abolished the protective effects of LXA 4 . Finally, both AKT and ERK inhibitors (LY294002 and UO126) blocked effects of LPS on the depression of ENaC-γ. However, LXA 4 only inhibited LPS-induced phosphorylation of AKT. In summary, LXA 4 activates ENaC-γ in part via the miR-21/PTEN/AKT signaling pathway.

As a minimally invasive and economical strategy, IHT is effective and equivalent to PE in achieving a fast reduction in TG levels. This article is protected by copyright. All rights reserved.