Protectin DX ameliorates inflammation in sepsis-induced acute lung injury through mediating PPARγ/NF-κB pathway

Previous reports have demonstrated that the newly identified lipid mediator protectin DX (PDX) could effectively attenuate multiple organ injuries in sepsis. The aim of our study was to clarify whether PDX could improve acute lung injury (ALI) induced by sepsis and elucidate the relevant potential mechanism. After inducing sepsis by the cecal ligation and puncture approach, mice were treated with a high or low dose of PDX. Pathological changes in the pulmonary tissue were analyzed by hematoxylin-eosin staining, and lung injury score was evaluated. Lung permeability and edema were assessed by lung wet/dry ratio, and protein and cellular load of the bronchoalveolar lavage fluid (BALF). Inflammatory cytokine levels in BALF were measured by ELISA and the expression of PPARγ in the lung tissue was analyzed by immunoblotting. The results suggested that PDX could diminish the inflammatory response in lung tissue after sepsis by upregulating PPARγ and inhibiting the phosphorylation and activation of NF-κB p65. PDX treatment lowered the levels of pro-inflammation cytokines IL-1β, IL-6, TNF-α, and MCP-1, and the levels of anti-inflammatory cytokine IL-10 was increased in the BALF. It also improved lung permeability and reduced lung injury. Furthermore, the protective effect of PDX on lung tissue could be reversed by GW9662, a specific PPAR-γ antagonist. Taken together, our study indicated that PDX could ameliorate the inflammatory response in ALI by activating the PPARγ/NF-κB pathway in a mouse model of sepsis.