Novel anti-inflammatory peptide alleviates liver ischemia-reperfusion injury

Area of Science:

• Immunology
• Hepatology
• Parasitology

Background:

• Ischemia-reperfusion injury (IRI) is a significant challenge in liver surgery, with macrophages implicated in its pathogenesis.
• The precise mechanisms by which macrophages influence IRI progression are not fully elucidated.

Purpose of the Study:

• To identify novel therapeutic agents for liver IRI.
• To investigate the role of schistosome egg-derived peptides in modulating macrophage function and mitigating IRI.

Main Methods:

• Target-guided screening of schistosome egg-derived peptides.
• In vivo mouse model of liver IRI.
• Macrophage depletion experiments.
• Transcriptomic sequencing (RNA-seq) to analyze signaling pathways.
• Western blotting to confirm pathway inhibition.

Main Results:

• A 3 kDa peptide, SjDX5-271, was identified that induces M2 macrophage polarization.
• SjDX5-271 treatment significantly protected mice against liver IRI, a benefit abolished by macrophage depletion.
• Transcriptomic analysis revealed inhibition of the Toll-like receptor (TLR) signaling pathway.
• SjDX5-271 was shown to inhibit the TLR4/MyD88/NF-κB signaling pathway, reducing hepatic inflammation.

Conclusions:

• SjDX5-271 demonstrates therapeutic potential for liver IRI by modulating macrophage polarization and suppressing inflammatory signaling.
• This study highlights the therapeutic promise of parasite-derived biologics and enhances understanding of host-parasite interactions.
• SjDX5-271 may offer a novel therapeutic strategy for IRI and other immune-related diseases.