There is no gold standard for evaluating the severity of community-acquired pneumonia (CAP), and it is still based on a score. This study aimed to use the metabolomics method to find promised biomarkers in assessing disease severity and potential therapeutic targets for CAP. The result found that the metabolites in the plasma samples of CAP patients had significantly different between the acute phase and the remission phase, especially lysophosphatidylcholine (LPCs) in glycerophospholipids, whose levels are negatively linked to the severity of the disease. Subsequently, the two key metabolites of myristoyl lysophosphatidylcholine (LPC 14:0) and LPC 16:1 were screened. We analyzed the predictive performance of the two metabolites using Spearman-related analysis and ROC curves, and LPC14:0 showed more satisfactory diagnostic performance than LPC16:1. Then we explored the protective role and mechanism of LPC 14:0 in animal and cell models. The results showed that LPC 14:0 could inhibit the LPS-induced secretion of IL-1β, IL-6, and TNF-α, lower the ROS and MDA levels, and decreased the depletion of SOD and GSH, thereby reducing lung tissue and cell damage, such as down-regulating the protein level in BALF, lung W/D ratio, MPO activity, and apoptosis. We found that LPC 14:0 inhibited LPS-induced inflammatory response and oxidative stress, and the above protection was achieved by inhibiting LPS-induced activation of the NLRP3 inflammasome. LPC 14:0 may serve as a novel biomarker for predicting the severity of CAP. In addition, our exploration of the role of LPC 14:0 in animal and cellular models has reinforced its promise as a therapeutic target to improve the clinical efficacy for CAP.
Keywords: Acute lung injury; Biomarker; Community-acquired pneumonia; Metabolomics; NLRP3 inflammasome.
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