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Updated: May 5, 2026

Cecal Ligation and Puncture-induced Sepsis as a Model To Study Autophagy in Mice
Published on: February 9, 2014
Sphinganine inhibits macrophage polarization and protects against sepsis-induced intestinal injury
Yi-Fan Chen1, Ze-Tian Wang2, Jian Zhao3
1Department of Trauma-Emergency and Critical Care Medicine Center, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, China.
Background:
Sepsis-induced intestinal injury disrupts barrier function and exacerbates systemic inflammation, contributing to high mortality.
Aim:
To investigate the mechanism by which sphinganine protects against sepsis-induced intestinal injury, focusing on macrophage polarization and toll like receptor 2 (TLR2)/nuclear factor kappa-B (NF-κB) signaling.
Methods:
A cecal ligation and puncture sepsis model was established in mice (n = 20/group). Treatments included sphinganine (15 mg/kg) and a TLR2 agonist [fibroblast-stimulating lipopeptide-1 (FSL-1), 10 μg/kg]. Serum markers [diamine oxidase (DAO), interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6] were measured by enzyme-linked immunosorbent assay. Intestinal injury and macrophage polarization [cluster of differentiation (CD) 86+ M1, CD206+ M2] were assessed via hematoxylin and eosin and immunofluorescence staining. Proteomic analysis, molecular docking, and Western blot were used to evaluate TLR2/NF-κB signaling. Data were analyzed by analysis of variance and t-test.
Results:
Sphinganine significantly reduced serum levels of DAO (P < 0.05), IL-1β, TNF-α, and IL-6 (P < 0.05), preserved intestinal crypt structure, and enhanced tight junction protein zonula occludens-1 expression. It promoted a shift from M1 (CD86+) to M2 (CD206+) macrophages. Proteomics identified TLR2 as the most differentially expressed protein, and molecular docking confirmed strong binding between sphinganine and TLR2 (-4.3 kcal/mol). Sphinganine downregulated TLR2 and phosphorylated-NF-κB p65 expression (P < 0.05), effects reversed by FSL-1. Total NF-κB p65 levels remained unchanged.
Conclusion:
Sphinganine protects against sepsis-induced intestinal injury by inhibiting TLR2/NF-κB signaling, modulating macrophage polarization toward the M2 phenotype, and preserving intestinal barrier integrity.
Insights
Sphinganine protects against sepsis-induced intestinal injury by reducing inflammation and preserving barrier function. It inhibits toll-like receptor 2 (TLR2)/nuclear factor kappa-B (NF-κB) signaling and promotes M2 macrophage polarization.
Area of Science:
- Immunology
- Gastroenterology
- Pharmacology
Background:
- Sepsis-induced intestinal injury compromises barrier function, worsening systemic inflammation and mortality.
- Understanding protective mechanisms is crucial for developing effective treatments.
Purpose of the Study:
- To elucidate how sphinganine mitigates sepsis-induced intestinal damage.
- Focus on sphinganine's effects on macrophage polarization and toll-like receptor 2 (TLR2)/nuclear factor kappa-B (NF-κB) signaling pathways.
Main Methods:
- A mouse model of sepsis (cecal ligation and puncture) was utilized.
- Sphinganine treatment effects on serum inflammatory markers, intestinal histology, macrophage phenotypes (M1/M2), and TLR2/NF-κB signaling were assessed.
- Proteomic analysis and molecular docking were employed to investigate molecular interactions.
Main Results:
- Sphinganine significantly decreased serum inflammatory cytokines (IL-1β, TNF-α, IL-6) and diamine oxidase (DAO).
- It preserved intestinal structure, enhanced tight junction protein expression, and shifted macrophage polarization towards the M2 phenotype.
- Sphinganine inhibited TLR2 and phosphorylated-NF-κB p65 expression, indicating suppression of the TLR2/NF-κB pathway.
Conclusions:
- Sphinganine confers protection against sepsis-induced intestinal injury.
- This protection is mediated by inhibiting TLR2/NF-κB signaling and promoting M2 macrophage polarization.
- Sphinganine preserves intestinal barrier integrity, offering a potential therapeutic strategy.
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