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.

PubMed
Abstract

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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