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This review aims to explore the molecular mechanisms and dual effects of pyroptosis in respiratory diseases.

May 19, 2026Open Access

Pyroptosis, A Double-Edged Sword in Respiratory Diseases: A Narrative Review

Key Points

This review aims to explore the molecular mechanisms and dual effects of pyroptosis in respiratory diseases.
Reviewed literature on pyroptosis and its pathways, focusing on acute lung injury, COPD, and lung cancer.
Examined recent findings on the gasdermin family and its pathological roles in cell death and inflammation.
Discussed therapeutic strategies aimed at modulating pyroptosis in respiratory diseases.
Pyroptosis contributes to both pathogen defense and excessive inflammation in respiratory conditions.
Evidence links dysregulated pyroptosis with diseases like asthma, COPD, and ARDS.
Therapeutic strategies targeting pyroptotic pathways show promise for clinical application.

Abstract

Chen Yu, 1, Caijun Dai, 1, Lujian Zhu2 1Department of Respiratory and Critical Care Medicine, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Peopleâs Republic of China; 2Department of Infectious Disease, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Peopleâs Republic of ChinaThese authors contributed equally to this workCorrespondence: Lujian Zhu, Department of Infectious Disease, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Peopleâs Republic of China, Email zhuljbrave@163. comAbstract: Pyroptosis is an inflammatory form of programmed cell death (PCD) driven by the gasdermin protein family. This process begins when danger- or damage-associated molecular patterns (DAMPs) are recognized, triggering either the canonical Caspase-1 or non-canonical Caspase-4/5/11 pathways. These pathways activate the cleavage of gasdermin D (GSDMD), releasing N-terminal fragments that form pores in cell membranes. This pore formation increases membrane permeability, leading to cell swelling and eventual lytic rupture. Pyroptosis serves as a double-edged sword in innate immunity: it defends against pathogens but can cause excessive inflammation and tissue damage if dysregulated. Evidence suggests that pyroptosis is involved in various respiratory diseases. The roles of pyroptosis and the Gasdermin family are complex, often exhibiting dual effects that complicate clinical interpretations. This review explores the molecular mechanisms and regulatory networks of pyroptosis, focusing on recent findings related to its role in pulmonary infections, acute lung injury (ALI) / acute respiratory distress syndrome (ARDS), allergic asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis (PF), and lung cancer. We also examine therapeutic strategies targeting pyroptotic pathways and recent advancements in their development, aiming to provide a theoretical foundation and new directions for mechanistic research and clinical translation in respiratory immune-inflammatory diseases. Keywords: pyroptosis, inflammasome, immuno-inflammation, respiratory diseases, therapeutic targets

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Chen et al. (Fri,) studied this question.

synapsesocial.com/papers/6a0bfd7a166b51b53d378d2a https://doi.org/https://doi.org/10.2147/jir.s601946

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