Affiliation:
1. Medical College of Jishou University, Jishou, P. R. China
Abstract
As severe conditions, acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) threaten human health. Inflammation and oxidative stress play a vital role in the pathogenesis of ALI/ARDS. Sphingosine kinase 1 (SphK1) significantly contributes to mediating inflammatory responses. Nevertheless, the impact of SphK1 on lipopolysaccharide (LPS)-triggered ALI/ARDS remains largely undetermined. In our current work, we explored the impact of SphK1 on ALI/ARDS using a mouse model. We studied whether it could reduce LPS-triggered inflammatory response and oxidative stress by suppressing SphK1 in ALI/ARDS. The mice were treated with the inhibitor of SphK1 (N,N-dimethylsphingosine, DMS) before intraperitoneal injection of LPS. Moreover, we assessed the survival rate, and several parameters, such as the lung wet/dry (W/D) ratio, myeloperoxidase (MPO) activity, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, and the release of inflammatory cytokines. Western blotting analysis was adopted to evaluate the levels of phosphoinositide 3-kinase (PI3K)/serine/threonine kinase (AKT) pathways. We showed that the inhibitor of SphK1 not only ameliorated LPS-stimulated lung histopathological changes and W/D ratio of lung tissue but also elevated the survival rate, the SOD activity and decreased the MDA content, MPO activity, interleukin-6 (IL-6) and tumor necrosis factor-ɑ (TNF-ɑ) production by regulating the PI3K/AKT signaling pathway in lung tissue. Taken together, SphK1 played an essential role in inflammatory responses and oxidative stress. The underlying mechanism might be linked to the activation and up-regulation of the PI3K/AKT signaling pathway in LPS-triggered ALI/ARDS.
Funder
Hunan Provincial Department of Education Research Project
Subject
Immunology,Immunology and Allergy,General Medicine