Protectin DX Ameliorates Sepsis-Induced Acute Lung Injury by Suppressing Neutrophil Activation via Inhibition of the MAPK/NF-B /p47phox-ser345 Signaling Pathway

Abstract Background Sepsis-induced acute lung injury (ALI) is one of the leading causes of death among critically ill patients. It is reported that Protectin DX (PDX), a kind of special pro-resolving mediator (SPM), has been recently discovered to contribute to the improvement of inflammatory diseases. However, its effect and mechanism on regulating ALI are still unknown. Methods We used C57BL/6J mice to construct ALI model via cecal ligation and puncture (CLP). Mice were injected intraperitoneally with saline or PDX one hour after modelling. We performed in-vitro experiments to explore the relationship between PDX and neutrophils. The neutrophils were isolated from healthy volunteers. They were treated with lipopolysaccharide (LPS) and different concentrations of PDX within one hour. Results We found that PDX can increase the survival rate of septic mice in eight days through the survival experiment, probably due to that PDX improved oxygenation of septic mice and alleviated sepsis-induced pathological lung injury and inflammation. Immunohistochemical and immunofluorescence experiments showed that PDX could effectively reduce the number of neutrophils in the lungs of septic mice. PDX reduced pro-inflammatory cytokines while attenuating sepsis-induced neutrophil activation. Moreover, western blotting results showed that PDX decreased the expression of MAPK (p38, ERK), NF-κB and p47phox-ser345 in lung tissue and neutrophils cultured in vitro. Conclusion Our experiments suggested that PDX can increase survival rate and reduce sepsis-induced ALI by inhibiting neutrophils activation via MAPK/NF-κB/p47phox-ser345 signaling pathway.