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Adoptive Transfer of IL-33-Stimulated Macrophages into Bleomycin-Induced Mouse Models to Study Their Effect on Idiopathic Pulmonary Fibrosis In Vivo
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Elamipretide(SS-31) Attenuates Idiopathic Pulmonary Fibrosis by Inhibiting the Nrf2-Dependent NLRP3 Inflammasome in

Yunjuan Nie1, Jiao Li1, Xiaorun Zhai1

  • 1Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.

Antioxidants (Basel, Switzerland)
|December 23, 2023
PubMed

Insights

Elamipretide (SS-31) peptide treatment significantly reduced pulmonary fibrosis and inflammation in a mouse model. This therapeutic effect is linked to the suppression of NLRP3 inflammasome activation via the Nrf2 pathway in macrophages.

Area of Science:

  • Pulmonary Medicine
  • Immunology
  • Mitochondrial Biology

Background:

  • Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with limited treatment options.
  • Mitochondrial oxidative stress in macrophages is a key factor in IPF pathogenesis.
  • Elamipretide (SS-31) is a mitochondrion-targeted peptide with demonstrated safety and efficacy in other diseases.

Purpose of the Study:

  • To investigate the therapeutic potential of Elamipretide (SS-31) in a bleomycin (BLM)-induced mouse model of pulmonary fibrosis.
  • To explore the underlying molecular mechanisms by which SS-31 may alleviate IPF.

Main Methods:

  • A bleomycin (BLM)-induced mouse model of pulmonary fibrosis was established.
  • Mice received SS-31 injections every other day.
  • Histological analysis, assessment of extracellular matrix deposition, inflammatory cytokine levels, and molecular pathway analysis (NLRP3 inflammasome, Nrf2) were performed in macrophages and lung tissues.

Main Results:

  • SS-31 treatment significantly attenuated BLM-induced pulmonary fibrosis and inflammation, improving histological outcomes.
  • SS-31 reduced extracellular matrix deposition and the release of inflammatory cytokines, including IL-1β and IL-18.
  • Mechanistically, SS-31 suppressed NLRP3 inflammasome activation and upregulated Nuclear factor erythroid 2-related factor 2 (Nrf2) expression, which was essential for its protective effects.

Conclusions:

  • Elamipretide (SS-31) demonstrates significant therapeutic efficacy against pulmonary fibrosis and inflammation in a preclinical model.
  • The protective mechanism involves the Nrf2-mediated inhibition of NLRP3 inflammasome activation in macrophages.
  • These findings support the potential of SS-31 as a novel therapeutic agent for Idiopathic Pulmonary Fibrosis (IPF).
Keywords:
IPFNLRP3 inflammasomeNrf2SS-31macrophage

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