Protective role of (5R)-5-hydroxytriptolide in lipopolysaccharide-induced acute lung injury by suppressing dendritic...

(5R)-5-hydroxytriptolide (LLDT-8) is a triptolide derivative with potent immunosuppressive property. This study aimed to investigate whether LLDT-8 manifests anti-inflammatory effects and influences dendritic cell function in early phase of lipopolysaccharide (LPS)-induced acute lung injury (ALI). C57BL/6 mice were administrated with LPS (6 mg/kg) to induce ALI and LLDT-8 were administrated at different doses (0.125 mg, 0.25 mg, 0.5 mg/kg). Histological changes were demonstrated by hematoxylin and eosin staining. Activation of dendritic cells were measured by flow cytometry. The concentrations of cytokines were measured by enzyme-linked immunosorbent assay. Bone marrow-derived dendritic cells (BMDCs) were acquired to explore immunosuppressive effects of LLDT-8 in vitro. Expression of Toll-like receptor 4 (TLR4), phosphorylation of inhibitor kappa B alpha (IκBα) and nuclear translocation of nuclear factor kappa B (NF-κB) were explored by immunoblot. Immunosuppressive property of LLDT-8-treated BMDCs were measured by adoptive transfer. The survival rate of ALI mice was significantly improved by LLDT-8 at the dose of 0.25 mg/kg. Moreover, systemic inflammatory response was suppressed and lung injury was relieved. LLDT-8 inhibited the activation of dendritic cells in vivo and influenced maturation, apoptosis and cytokine secretion capacity of BMDCs in vitro. Additionally, LLDT-8-treated BMDCs manifested reduced expression of TLR4, phosphorylation of IκBα and nuclear translocation of NF-κB. Adoptive transfer of LLDT-8-treated BMDCs alleviated LPS-induced lung injury. LLDT-8 also had protective effects on Pseudomonas aeruginosa-induced ALI. In conclusion, LLDT-8 played a protective role against ALI and suppressed dendritic cell activation potentially through affecting TLR4 expression and NF-κB signaling.