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Updated: Jan 15, 2026
Inducing Acute Lung Injury in Mice by Direct Intratracheal Lipopolysaccharide Instillation
Published on: July 6, 2019
10-Hydroxy-2-decenoic acid ameliorates LPS-induced acute lung injury through targeting MD2-mediated inflammatory
Cong Shu1, Chen Li1, Huamin Liu1
1School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
Background:
Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), are life-threatening conditions with high mortality, characterized by excessive inflammatory responses. Lipopolysaccharide (LPS) is widely used to mimic ALI by activating myeloid differentiation factor 2 (MD2)/Toll-like receptor 4 (TLR4)-mediated inflammatory pathways. Royal jelly-derived 10-hydroxy-2-decenoic acid (10-HDA) exhibits anti-inflammatory properties, but its role in ALI remains unexplored.
Objective:
This study aimed to investigate the therapeutic potential of 10-HDA against LPS-induced ALI and elucidate its underlying mechanism.
Methods:
In vitro, mouse peritoneal macrophages (MPMs) were pretreated with 10-HDA before LPS stimulation. In vivo, ALI was induced in mice via intratracheal LPS, with 10-HDA administered intraperitoneally. Cytokine levels were measured via ELISA and qPCR. Signaling pathways were analyzed by Western blot and immunofluorescence. Lung injury, inflammatory cell infiltration, and edema were assessed via histopathology, BALF analysis, and wet/dry ratio. Immunoprecipitation, molecular docking, and drug affinity-responsive target stability (DARTS) assays were used to identify the interaction between 10-HDA and MD2.
Results:
10-HDA significantly suppressed LPS-induced proinflammatory cytokine secretion in MPMs and ALI mice, and inhibited phosphorylation of TAK1, MAPKs, TBK1 and NF-κB nuclear translocation. It attenuated lung histopathological damage, neutrophil infiltration, and edema. Mechanistically, 10-HDA disrupted MD2/TLR4-mediated inflammatory pathways by directly binding MD2, as confirmed by immunoprecipitation, DARTS, and molecular docking.
Conclusion:
10-HDA alleviates LPS-induced ALI by targeting MD2 to block TLR4 signaling, thereby suppressing both MyD88-dependent (MAPKs/NF-κB) and TRIF-dependent (TBK1/IRF3) pathways. These findings highlight 10-HDA as a promising therapeutic candidate for ALI/ARDS.
