LTB4 Promotes Acute Lung Injury via Upregulating the PLCε-1/TLR4/NF-κB Pathway in One-Lung Ventilation

Background. Mechanical ventilation (MV) can provoke acute lung injury (ALI) by increasing inflammation activation and disrupting the barrier in lung tissues even causing death. However, the inflammation-related molecules and pathways in MV-induced ALI remain largely unknown. Hence, the purposes of this study are to examine the role and mechanism of a novel inflammation-related molecule, leukotriene B4 (LTB4), in ALI. Methods. The functions of LTB4 in one-lung ventilation (OLV) model were detected by the loss-of-function experiments. H&E staining was used to examine the pathologic changes of lung tissues. Functionally, PLC epsilon-1 knockdown and Toll-like receptor 4 (TLR4)/NF-kappa B pathway inhibitor were used to detect the regulatory effects of LTB4 on the phospholipase C epsilon (PLC epsilon-1)/TLR4/nuclear factor-kappa B (NF-kappa B) pathway. The levels of genes and proteins were determined by RT-qPCR and western blotting assay. The levels of inflammation cytokines and chemokines were measured by ELISA. Results. Here, we found LTA4H, leukotriene B (4) receptor 1 (BLT1), LTB4, and PLC epsilon-1 upregulated in OLV rats and associated with inflammatory activation and lung permeability changes of lung tissues. Inhibition of LTB4 alleviated the OLV-induced ALI by inhibiting inflammatory activation and lung permeability changes of lung tissues. For mechanism analyses, LTB4 promoted OLV-induced ALI by activating the PLC epsilon-1/TLR4/NF-kappa B pathway. Conclusion. LTB4 induced ALI in OLV rats by activating the PLC epsilon-1/TLR4/NF-kappa B pathway. Our findings might supply a new potential therapeutic for OLV-induced ALI.

Automated summary

This study demonstrates that leukotriene B4 (LTB4) is upregulated in one-lung ventilation (OLV) rats and plays a role in activating the PLC epsilon-1/TLR4/NF-kappa B pathway, leading to acute lung injury (ALI). Inhibition of LTB4 can alleviate ALI induced by OLV, suggesting a potential therapeutic target for OLV-induced ALI.