Evidence map›Paper›PMID 42478233›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

Membrane-Active Peptide Protects Against Inflammation by Targeting NLRP3 Activation at the Trans-Golgi Network.

Jonas Engelhardt, Nico Kirsch, Aileen Kerfin, Lars P Lunding, Dominic Ferber, Hannes Buthmann, Ilka Schreier, Carlotta Bosio, Ann-Kathrin Dobbelstein, Anna Klawonn and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Jonas EngelhardtPharmaceutical Institute, Section Pharmacology and Toxicology, University of Bonn, Bonn, Germany.
Nico KirschPharmaceutical Institute, Section Pharmacology and Toxicology, University of Bonn, Bonn, Germany.ORCID https://orcid.org/0009-0009-9041-4699
Aileen KerfinDivision of Immunobiophysics, Priority Area Infections, Research Center Borstel, Leibniz Lung Center, Member of Leibniz Health Technologies, Borstel, Germany.
Lars P LundingDivision of Lung Immunology, Priority Area Chronic Lung Diseases, Research Center Borstel, Leibniz Lung Center, Borstel, Germany.ORCID https://orcid.org/0000-0002-5278-3129
Dominic FerberInstitute of Structural Biology, University of Bonn, Bonn, Germany.ORCID https://orcid.org/0000-0003-2633-2858
Hannes ButhmannInstitute of Structural Biology, University of Bonn, Bonn, Germany.ORCID https://orcid.org/0009-0007-8231-1791
Ilka SchreierPharmaceutical Institute, Section Pharmacology and Toxicology, University of Bonn, Bonn, Germany.
Carlotta BosioPharmaceutical Institute, Section Pharmacology and Toxicology, University of Bonn, Bonn, Germany.
Ann-Kathrin DobbelsteinPharmaceutical Institute, Section Pharmacology and Toxicology, University of Bonn, Bonn, Germany.
Anna KlawonnPharmaceutical Institute, Section Pharmacology and Toxicology, University of Bonn, Bonn, Germany.
Rebecca C CollWellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, UK.ORCID https://orcid.org/0000-0002-7359-6023
Lena BauernhoferBiophysics, Institute of Molecular Biosciences (IMB), NAWI Graz, University of Graz, Graz, Austria.ORCID https://orcid.org/0000-0001-9980-9683
Sandro KellerBiophysics, Institute of Molecular Biosciences (IMB), NAWI Graz, University of Graz, Graz, Austria.ORCID https://orcid.org/0000-0001-5469-8772
Matthias GeyerInstitute of Structural Biology, University of Bonn, Bonn, Germany.ORCID https://orcid.org/0000-0002-7718-5002
Michael WegmannDivision of Lung Immunology, Priority Area Chronic Lung Diseases, Research Center Borstel, Leibniz Lung Center, Borstel, Germany.ORCID https://orcid.org/0000-0002-1658-1554
Andra B SchrommDivision of Immunobiophysics, Priority Area Infections, Research Center Borstel, Leibniz Lung Center, Member of Leibniz Health Technologies, Borstel, Germany.ORCID https://orcid.org/0000-0002-2606-3515
Günther WeindlPharmaceutical Institute, Section Pharmacology and Toxicology, University of Bonn, Bonn, Germany.ORCID https://orcid.org/0000-0002-4493-7597

Funding

Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) EXC2151-390873048Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) GE976/16-1Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) GRK2873(494832089)European Research Council (ERC Advanced Grant) NalpACTLeibniz Research Alliance 'Leibniz Health Technologies' FFS 55Studienstiftung des deutschen Volkes, Bonn, Germany
6 · The paper itself

Abstract

The NLRP3 inflammasome is a multi-protein complex that plays a crucial role in inflammatory processes mediated by the innate immune system. Dysregulated NLRP3 activation has been implicated in age-related inflammatory diseases, making it a promising therapeutic target. Here, we report that the synthetic membrane-active antimicrobial peptide Pep19-2.5 directly inhibits NLRP3 inflammasome activation. Through cellular, biophysical, and biochemical analyses, we find that Pep19-2.5 suppresses NLRP3 inflammasome signaling downstream of NLRP3 activation. Pep19-2.5 interacts with macrophage membranes, supporting a membrane-targeting mechanism for its anti-inflammatory effects. Mechanistically, Pep19-2.5 binds to phosphatidylinositol (PI)-containing lipid membranes and dispersed trans-Golgi network (dTGN) structures, which could potentially affect NLRP3 recruitment to the dTGN. We demonstrate a strong and NLRP3-dependent induction of IL-1β secretion from human macrophages by house dust mite (HDM) extract, which can be inhibited by Pep19-2.5. In line with these findings, therapeutic application of Pep19-2.5 via the nasal aerosol route reduces IL-1β levels, eosinophil infiltration in bronchoalveolar lavage and significantly improved lung function in an in vivo HDM-mouse model of allergic airway inflammation. Our findings highlight the therapeutic potential of targeting NLRP3 activation by the small membrane-active peptide Pep19-2.5 for the treatment of NLRP3-driven inflammatory diseases.

Indexed as

InflammasomesInflammationNLR Family, Pyrin Domain-Containing 3 ProteinPeptidestrans-Golgi NetworkAnimalsHumansInterleukin-1betaMacrophagesMiceInflammasomesInterleukin-1betaNLR Family, Pyrin Domain-Containing 3 ProteinNLRP3 protein, humanPeptidesallergic airway inflammationasthmainterleukin‐1betamembrane‐active peptideNLRP3 inflammasomePep19‐2.5

Identifiers

PMID42478233
PMCPMC13386142

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.