Related Experiment Video
Updated: Jul 4, 2026
Evaluation of a Reliable Biomarker in a Cecal Ligation and Puncture-Induced Mouse Model of Sepsis
Published on: December 9, 2022
Choline supplementation protects against sepsis-induced lung injury, potentially through suppression of
Li-Ming Xu1, Wei-Can Chen1, Zhen-Dong Sun1
1Department of Anesthesiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
Objective:
Choline supplementation has been implicated in the regulation of inflammation and immune responses. This study aimed to investigate the protective effects of choline supplementation in sepsis-induced lung injury (SLI) and to elucidate the underlying mechanisms.
Methods:
SLI was induced in mice via cecal ligation and puncture (CLP). Serum choline levels were measured, and choline supplementation effects were evaluated in vivo. Integrated transcriptomic and proteomic analyses identified potential targets and pathways. Public single-cell RNA sequencing data determined the cellular distribution of candidate genes. In vitro assays in THP-1 cells were performed to validate the role of key targets.
Results:
Compared with Sham controls, SLI mice exhibited significantly decreased serum choline levels. The SLI mouse model exhibited typical pathological features, including pulmonary hemorrhage, interstitial edema, alveolar wall thickening, elevated inflammatory cytokines, and increased lung injury scores, all of which were significantly alleviated by choline supplementation. Multi-omics analyses identified Prtn3 as a potential target associated with the protective effects of choline. Single-cell analysis suggested that Prtn3 is predominantly expressed in monocyte/macrophage populations. In vitro, choline treatment attenuated LPS-induced inflammatory responses and chemotactic activity in THP-1 cells, accompanied by reduced expression of IL-1β, IL-6, TNF-α, Prtn3 and NF-κB pathway proteins. Prtn3 overexpression partially reversed the inhibitory effects of choline on cytokine production, monocyte migration, and NF-κB pathway activation. Conversely, pharmacological inhibition of Prtn3 by sivelestat suppressed inflammatory cytokine expression and attenuated NF-κB signaling under LPS-stimulated conditions.
Conclusion:
Choline supplementation protects against SLI by suppressing monocyte inflammatory activation, at least in part through inhibition of the Prtn3-dependent NF-κB signaling pathway. These findings suggest that targeting the choline-Prtn3-NF-κB axis may represent a potential therapeutic strategy for sepsis-associated lung injury.
