Accelerated inflammation and oxidative stress induced by LPS in acute lung injury: Inhibition by ST1926

Abstract

Bioavailable and less toxic synthetic retinoids, such as the atypical adamantyl retinoid ST1926, have been well developed and investigated in clinical trials for many diseases. The aim of our study was to explore the role of ST1926 in lipopolysaccharide (LPS)-induced acute lung injury (ALI) and to reveal the possible molecular mechanism. Mice were treated with LPS to induce acute lung injury followed by ST1926 administration. After LPS induction, mice administered with ST1926 showed lower inflammation infiltration in bronchoalveolar lavage (BAL) fluid, and pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-18, IL-6 and tumor necrosis factor-α (TNF-α) in serum and lung tissue samples obtained from mice. In addition, western blot assays suggested that ST1926 suppressed nuclear factor-κB (NF-κB), inhibitor-κB kinase-α (IκBα) and IκB kinase (IKKα), as well as Toll-like receptor 4 (TLR4) induced by LPS. In addition, reactive oxygen species (ROS) stimulated by LPS was also suppressed for ST1926 through inhibiting p38 and extracellular receptor kinase (ERK) signaling pathway. Taken together, the data here indicated that ST1926 may be of potential value in treating acute lung injury through inflammation and ROS suppression via inactivating TLR4/NF-κB and p38/ERK1/2 signaling pathways.