Elamipretide(SS-31) Attenuates Idiopathic Pulmonary Fibrosis by Inhibiting the Nrf2-Dependent NLRP3 Inflammasome in Macrophages.

Nie Y, Li J, Zhai X, Wang Z, Wang J, Wu Y, Zhao P, Yan G

Antioxidants (Basel, Switzerland)21 Nov 2023Cited by 25 (Europe PMC)

PMID38136142PMCIDPMC10740969DOI10.3390/antiox12122022PepBankPUB-38136142

Summary

Idiopathic pulmonary fibrosis (IPF) is a progressive fatal lung disease with a limited therapeutic strategy. Mitochondrial oxidative stress in macrophages is directly linked to IPF. Elamipretide(SS-31) is a mitochondrion-targeted peptide that has been shown to be safe and beneficial for multiple diseases. However, whether SS-31 alleviates IPF is unclear. In the present study, we used a bleomycin (BLM)-induced mouse model followed by SS-31 injection every other day to investigate its role in IPF and explore the possible mechanism. Our results showed that SS-31 treatment significantly suppressed BLM-induced pulmonary fibrosis and inflammation, with improved histological change, and decreased extracellular matrix deposition and inflammatory cytokines release. Impressively, the expression percentage of IL-1β and IL-18 was downregulated to lower than half with SS-31 treatment. Mechanistically, SS-31 inhibited IL-33- or lipopolysaccharide(LPS)/IL-4-induced production of IL-1β and IL-18 in macrophages by suppressing NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome activation. Nuclear factor erythroid 2-related factor 2(Nrf2) was dramatically upregulated along with improved mitochondrial function after SS-31 treatment in activated macrophages and BLM-induced mice. Conversely, there was no significant change after SS-31 treatment in Nrf2-/- mice and macrophages. These findings indicated that SS-31 protected against pulmonary fibrosis and inflammation by inhibiting the Nrf2-mediated NLRP3 inflammasome in macrophages. Our data provide initial evidence for the therapeutic efficacy of SS-31 in IPF.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study14

14 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In mice with bleomycin-induced lung injury, SS‑31 significantly suppressed pulmonary fibrosis.
In plain wordsIn mice with lung fibrosis, SS‑31 reduced the fibrosis.
Peptide
Elamipretide (SS-31)
Outcome
DecreasePulmonary fibrosis
Study
mousen: not reported in source
Bleomycin-induced pulmonary fibrosis
Outcome group
Lung injury and fibrosis · Respiratory
Studied dose
Dose not stated
Source sentences
Summary
SS-31 treatment significantly suppressed BLM-induced pulmonary fibrosis and inflammation
1 context sentence(design, population, supporting numbers)
Summary · context
In the present study, we used a bleomycin (BLM)-induced mouse model followed by SS-31 injection every other day to investigate its role in IPF and explore the possible mechanism.
Show in the study text Report a problemFND-3813614201
02AnimalAnimal study (in vivo)Efficacy outcome
In mice with bleomycin-induced lung injury, SS‑31 significantly suppressed pulmonary inflammation.
In plain wordsIn mice with lung fibrosis, SS‑31 reduced lung inflammation.
Peptide
Elamipretide (SS-31)
Outcome
DecreasePulmonary inflammation
Study
mousen: not reported in source
Bleomycin-induced pulmonary fibrosis
Outcome group
Inflammation markers · Respiratory
Studied dose
Dose not stated
Source sentences
Summary
SS-31 treatment significantly suppressed BLM-induced pulmonary fibrosis and inflammation
1 context sentence(design, population, supporting numbers)
Summary · context
In the present study, we used a bleomycin (BLM)-induced mouse model followed by SS-31 injection every other day to investigate its role in IPF and explore the possible mechanism.
Show in the study text Report a problemFND-3813614202
03AnimalAnimal study (in vivo)Efficacy outcome
In mice with bleomycin-induced lung injury, SS‑31 treatment was accompanied by improved histological change.
In plain wordsIn mice with lung fibrosis, lung tissue looked better under the microscope after SS‑31.
Peptide
Elamipretide (SS-31)
Outcome
Not applicableHistological change
Study
mousen: not reported in source
Bleomycin-induced pulmonary fibrosis
Outcome group
Lung injury and fibrosis · Respiratory
Studied dose
Dose not stated
Source sentences
Summary
with improved histological change, and decreased extracellular matrix deposition and inflammatory cytokines release.
1 context sentence(design, population, supporting numbers)
Summary · context
In the present study, we used a bleomycin (BLM)-induced mouse model followed by SS-31 injection every other day to investigate its role in IPF and explore the possible mechanism.
Show in the study text Report a problemFND-3813614203
04AnimalAnimal study (in vivo)Efficacy outcome
In mice with bleomycin-induced lung injury, SS‑31 decreased extracellular matrix deposition.
In plain wordsIn mice with lung fibrosis, SS‑31 reduced scar-like matrix build-up in the lung.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseExtracellular matrix deposition
Study
mousen: not reported in source
Bleomycin-induced pulmonary fibrosis
Outcome group
Lung injury and fibrosis · Respiratory
Studied dose
Dose not stated
Source sentences
Summary
SS-31 treatment significantly suppressed BLM-induced pulmonary fibrosis and inflammation, with improved histological change, and decreased extracellular matrix deposition and inflammatory cytokines release
1 context sentence(design, population, supporting numbers)
Summary · context
In the present study, we used a bleomycin (BLM)-induced mouse model followed by SS-31 injection every other day to investigate its role in IPF and explore the possible mechanism.
Show in the study text Report a problemFND-3813614204
05AnimalAnimal study (in vivo)Efficacy outcome
In mice with bleomycin-induced lung injury, SS‑31 decreased the release of inflammatory cytokines.
In plain wordsIn mice with lung fibrosis, SS‑31 lowered the release of inflammation signals.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseInflammatory cytokine release
Study
mousen: not reported in source
Bleomycin-induced pulmonary fibrosis
Outcome group
Inflammation markers · Respiratory
Studied dose
Dose not stated
Source sentences
Summary
SS-31 treatment significantly suppressed BLM-induced pulmonary fibrosis and inflammation, with improved histological change, and decreased extracellular matrix deposition and inflammatory cytokines release
1 context sentence(design, population, supporting numbers)
Summary · context
In the present study, we used a bleomycin (BLM)-induced mouse model followed by SS-31 injection every other day to investigate its role in IPF and explore the possible mechanism.
Show in the study text Report a problemFND-3813614205
06AnimalAnimal study (in vivo)Efficacy outcome
In mice with bleomycin-induced lung injury, SS‑31 lowered the expression percentage of IL-1β and IL-18 to less than half.
In plain wordsIn mice with lung fibrosis, SS‑31 cut IL-1β and IL-18 expression to less than half.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseIL-1β and IL-18 expression
Study
mousen: not reported in source
Bleomycin-induced pulmonary fibrosis
Outcome group
Inflammation markers · Respiratory
Studied dose
Dose not stated
Source sentences
Summary
Impressively, the expression percentage of IL-1β and IL-18 was downregulated to lower than half with SS-31 treatment.
1 context sentence(design, population, supporting numbers)
Summary · context
In the present study, we used a bleomycin (BLM)-induced mouse model followed by SS-31 injection every other day to investigate its role in IPF and explore the possible mechanism.
Show in the study text Report a problemFND-3813614206
07AnimalAnimal study (in vivo)Mechanism
In bleomycin-induced mice, SS‑31 treatment upregulated Nrf2.
In plain wordsIn mice with lung fibrosis, SS‑31 raised levels of the protein Nrf2.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseNrf2 expression in BLM mice
Study
mousen: not reported in source
Bleomycin-induced pulmonary fibrosis
Outcome group
Receptor activity and mechanism · Respiratory
Studied dose
Dose not stated
Source sentences
Summary
Nuclear factor erythroid 2-related factor 2(Nrf2) was dramatically upregulated along with improved mitochondrial function after SS-31 treatment in activated macrophages and BLM-induced mice.
1 context sentence(design, population, supporting numbers)
Summary · context
In the present study, we used a bleomycin (BLM)-induced mouse model followed by SS-31 injection every other day to investigate its role in IPF and explore the possible mechanism.
Show in the study text Report a problemFND-3813614210
08AnimalAnimal study (in vivo)Mechanism
In bleomycin-induced mice, SS‑31 treatment improved mitochondrial function.
In plain wordsIn mice with lung fibrosis, SS‑31 improved mitochondrial function.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseMitochondrial function in BLM mice
Study
mousen: not reported in source
Bleomycin-induced pulmonary fibrosis
Outcome group
Mitochondrial function · Respiratory
Studied dose
Dose not stated
Source sentences
Summary
Nuclear factor erythroid 2-related factor 2(Nrf2) was dramatically upregulated along with improved mitochondrial function after SS-31 treatment in activated macrophages and BLM-induced mice.
1 context sentence(design, population, supporting numbers)
Summary · context
In the present study, we used a bleomycin (BLM)-induced mouse model followed by SS-31 injection every other day to investigate its role in IPF and explore the possible mechanism.
Show in the study text Report a problemFND-3813614212
09AnimalAnimal study (in vivo)Mechanism
In Nrf2-deficient mice, SS‑31 treatment produced no significant change.
In plain wordsIn mice lacking Nrf2, SS‑31 produced no significant change.
Peptide
Elamipretide (SS-31)
Outcome
No significant changeSS-31 effect in Nrf2-deficient mice
Study
mousen: not reported in source
Nrf2-/- mice
Outcome group
Receptor activity and mechanism · Respiratory
Studied dose
Dose not stated
Source sentences
Summary
Conversely, there was no significant change after SS-31 treatment in Nrf2-/- mice and macrophages.
1 context sentence(design, population, supporting numbers)
Summary · context
In the present study, we used a bleomycin (BLM)-induced mouse model followed by SS-31 injection every other day to investigate its role in IPF and explore the possible mechanism.
Show in the study text Report a problemFND-3813614213
10LabIn vitro (cells)Mechanism
In macrophages, SS‑31 inhibited IL-33- or LPS/IL-4-induced production of IL-1β and IL-18.
In plain wordsIn macrophages, SS‑31 lowered the production of IL-1β and IL-18.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseIL-1β and IL-18 production in macrophages
Study
n: not reported in source
Macrophages stimulated with IL-33 or LPS/IL-4
Outcome group
Inflammation markers · Respiratory
Studied dose
Dose not stated
Source sentences
Summary
Mechanistically, SS-31 inhibited IL-33- or lipopolysaccharide(LPS)/IL-4-induced production of IL-1β and IL-18 in macrophages by suppressing NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome activation.
Show in the study text Report a problemFND-3813614207
11LabIn vitro (cells)Mechanism
In macrophages, SS‑31 suppressed NLRP3 inflammasome activation.
In plain wordsIn macrophages, SS‑31 reduced activation of the NLRP3 inflammasome.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseNLRP3 inflammasome activation in macrophages
Study
n: not reported in source
Macrophages stimulated with IL-33 or LPS/IL-4
Outcome group
Inflammation markers · Respiratory
Studied dose
Dose not stated
Source sentences
Summary
Mechanistically, SS-31 inhibited IL-33- or lipopolysaccharide(LPS)/IL-4-induced production of IL-1β and IL-18 in macrophages by suppressing NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome activation.
Show in the study text Report a problemFND-3813614208
12LabIn vitro (cells)Mechanism
In activated macrophages, SS‑31 treatment upregulated Nrf2.
In plain wordsIn macrophages, SS‑31 raised levels of the protein Nrf2.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseNrf2 expression in macrophages
Study
n: not reported in source
Activated macrophages
Outcome group
Receptor activity and mechanism · Respiratory
Studied dose
Dose not stated
Source sentences
Summary
Nuclear factor erythroid 2-related factor 2(Nrf2) was dramatically upregulated along with improved mitochondrial function after SS-31 treatment in activated macrophages and BLM-induced mice.
Show in the study text Report a problemFND-3813614209
13LabIn vitro (cells)Mechanism
In activated macrophages, SS‑31 treatment improved mitochondrial function.
In plain wordsIn macrophages, SS‑31 improved mitochondrial function.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseMitochondrial function in macrophages
Study
n: not reported in source
Activated macrophages
Outcome group
Mitochondrial function · Respiratory
Studied dose
Dose not stated
Source sentences
Summary
Nuclear factor erythroid 2-related factor 2(Nrf2) was dramatically upregulated along with improved mitochondrial function after SS-31 treatment in activated macrophages and BLM-induced mice.
Show in the study text Report a problemFND-3813614211
14LabIn vitro (cells)Mechanism
In Nrf2-deficient macrophages, SS‑31 treatment produced no significant change.
In plain wordsIn macrophages lacking Nrf2, SS‑31 produced no significant change.
Peptide
Elamipretide (SS-31)
Outcome
No significant changeSS-31 effect in Nrf2-deficient macrophages
Study
n: not reported in source
Nrf2-/- macrophages
Outcome group
Receptor activity and mechanism · Respiratory
Studied dose
Dose not stated
Source sentences
Summary
Conversely, there was no significant change after SS-31 treatment in Nrf2-/- mice and macrophages.
Show in the study text Report a problemFND-3813614214

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

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Version 2Current
10 Oct 2026, 08:19 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

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