LTB4 Promotes Acute Lung Injury via Upregulating the PLC ε -1/TLR4/NF- κ B 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 ε -1 knockdown and Toll-like receptor 4 (TLR4)/NF- κ B pathway inhibitor were used to detect the regulatory effects of LTB4 on the phospholipase C ε (PLC ε -1)/TLR4/nuclear factor-kappa B (NF- κ 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 ε -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 ε -1/TLR4/NF- κ B pathway.
Conclusion: LTB4 induced ALI in OLV rats by activating the PLC ε -1/TLR4/NF- κ B pathway. Our findings might supply a new potential therapeutic for OLV-induced ALI.
Competing Interests: The authors declare no conflict of interest.
(Copyright © 2022 Jing Luo et al.)