Pranindya-Sari Astari, Susanto Agus Dwi, Indarto Dono, Dirgahayu Paramasari
Doctoral Program of Medical Science, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia.
Universitas Gadjah Mada (UGM) Academic Hospital, Yogyakarta, Indonesia.
Nicotine Tob Res. 2025 Jul 3. doi: 10.1093/ntr/ntaf140.
Cigarette smoke (CS) is a major contributor to respiratory and systemic diseases, primarily due to its ability to induce cellular damage and chronic inflammation. While apoptosis has long been recognised as the dominant form of cell death resulting from CS exposure, recent findings highlight pyroptosis-a caspase-1 (CASP-1)-dependent, pro-inflammatory form of programmed cell death-as a key pathological mechanism. Pyroptosis is characterised by gasdermin D (GSDMD) cleavage, pore formation in the cell membrane, and the release of inflammatory cytokines, particularly interleukin (IL)-1β and IL-18.
This review synthesises evidence from peer-reviewed articles published between 2014 and 2024, identified through searches in PubMed, Scopus, Web of Science, and Google Scholar. Search terms included "pyroptosis", "cigarette smoke", "inflammasome", "caspase-1", and "gasdermin D". Only English-language articles from reputable, Scopus-indexed journals were included. Studies focusing on pyroptotic mechanisms, disease progression, and therapeutic interventions were prioritised.
Numerous studies demonstrate that CS activates inflammasomes, triggering CASP-1 activation and GSDMD-mediated pyroptosis. This mechanism exacerbates chronic pulmonary diseases such as COPD and emphysema and also plays a role in extrapulmonary conditions including atherosclerosis, liver dysfunction, and neuroinflammation. Inhibitors of CASP-1 and inflammasome components, as well as natural bioactive compounds, have shown potential in suppressing pyroptotic pathways and alleviating CS-induced tissue damage.
Pyroptosis represents a critical inflammatory pathway in CS-induced diseases. Targeting inflammasome signalling and pyroptotic mediators offers a promising strategy for therapeutic development. A deeper understanding of this cell death mechanism could inform novel interventions to combat the widespread impact of smoking-related pathology.
This review elucidates the critical role of pyroptosis as a key inflammatory mechanism in response to the toxic effects of cigarette exposure. By synthesizing recent scientific evidence, it underscores the involvement of pyroptotic pathways in the pathogenesis of tobacco-related diseases, highlighting their contribution to tissue damage and disease progression. A deeper understanding of these mechanisms may facilitate the identification of novel therapeutic targets aimed at mitigating the detrimental health effects of cigarette smoke. These insights could further inform the development of preventive and therapeutic strategies to alleviate the inflammatory burden associated with chronic cigarette exposure.
香烟烟雾（CS）是导致呼吸系统和全身性疾病的主要因素，主要是因为它能够引发细胞损伤和慢性炎症。虽然长期以来细胞凋亡一直被认为是CS暴露导致的主要细胞死亡形式，但最近的研究结果突出了焦亡——一种依赖半胱天冬酶 -1（CASP-1）的促炎性程序性细胞死亡形式——作为一种关键的病理机制。焦亡的特征是gasdermin D（GSDMD）裂解、细胞膜上形成孔道以及炎性细胞因子的释放，特别是白细胞介素（IL）-1β和IL-18。
本综述综合了2014年至2024年间发表的同行评审文章中的证据，这些文章通过在PubMed、Scopus、科学网和谷歌学术上进行检索而确定。检索词包括“焦亡”、“香烟烟雾”、“炎性小体”、“半胱天冬酶 -1”和“gasdermin D”。仅纳入来自知名的、被Scopus索引的期刊的英文文章。重点关注焦亡机制、疾病进展和治疗干预的研究被优先考虑。
大量研究表明，CS激活炎性小体，触发CASP-1激活和GSDMD介导的焦亡。这一机制加剧了慢性肺部疾病，如慢性阻塞性肺疾病（COPD）和肺气肿，并且在包括动脉粥样硬化、肝功能障碍和神经炎症在内的肺外病症中也起作用。CASP-1和炎性小体成分的抑制剂以及天然生物活性化合物已显示出抑制焦亡途径和减轻CS诱导的组织损伤的潜力。
焦亡是CS诱导疾病中的关键炎症途径。靶向炎性小体信号传导和焦亡介质为治疗开发提供了一种有前景的策略。对这种细胞死亡机制的更深入理解可为对抗吸烟相关病理的广泛影响的新干预措施提供依据。
本综述阐明了焦亡作为对香烟暴露毒性作用的关键炎症机制的重要作用。通过综合近期的科学证据，强调了焦亡途径在烟草相关疾病发病机制中的参与，突出了它们对组织损伤和疾病进展的贡献。对这些机制的更深入理解可能有助于确定旨在减轻香烟烟雾有害健康影响的新治疗靶点。这些见解可进一步为预防和治疗策略的开发提供信息，以减轻与长期香烟暴露相关的炎症负担。
