VX-765 attenuates silica-induced lung inflammatory injury and fibrosis by modulating alveolar macrophages pyroptosis in mice

Tao, Huihui; Mo, Aowei; Shao, Luocheng; Ge, Deyong; Liu, Jiale; Hu, Wenjian; Xu, Ke; Ma, Qianqian; Wang, Wenfeng; Wang, Qianqian; Cao, Hangbing; Mu, Min; Tao, Xinrong; Wang, Jianhua

doi:10.1016/j.ecoenv.2022.114359

Cited by 14 publications

(5 citation statements)

References 32 publications

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“… [ 73 ] Vx-765 It can inhibit caspase-1. [ 74 ] Jujuboside A It works by blocking inflammasome-mediated pyroptosis. [ 75 ] Mcc950 It targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition.…”

Section: Factors Affecting Rt-induced Pyroptosismentioning

confidence: 99%

Pyroptotic cell death: an emerging therapeutic opportunity for radiotherapy

Li,

Yang,

Zhang

et al. 2024

Cell Death Discov.

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Pyroptotic cell death, an inflammatory form of programmed cell death (PCD), is emerging as a potential therapeutic opportunity for radiotherapy (RT). RT is commonly used for cancer treatment, but its effectiveness can be limited by tumor resistance and adverse effects on healthy tissues. Pyroptosis, characterized by cell swelling, membrane rupture, and release of pro-inflammatory cytokines, has been shown to enhance the immune response against cancer cells. By inducing pyroptotic cell death in tumor cells, RT has the potential to enhance treatment outcomes by stimulating anti-tumor immune responses and improving the overall efficacy of RT. Furthermore, the release of danger signals from pyroptotic cells can promote the recruitment and activation of immune cells, leading to a systemic immune response that may target distant metastases. Although further research is needed to fully understand the mechanisms and optimize the use of pyroptotic cell death in RT, it holds promise as a novel therapeutic strategy for improving cancer treatment outcomes. This review aims to synthesize recent research on the regulatory mechanisms underlying radiation-induced pyroptosis and to elucidate the potential significance of this process in RT. The insights gained from this analysis may inform strategies to enhance the efficacy of RT for tumors.

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Section: Factors Affecting Rt-induced Pyroptosismentioning

confidence: 99%

Pyroptotic cell death: an emerging therapeutic opportunity for radiotherapy

Li,

Yang,

Zhang

et al. 2024

Cell Death Discov.

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“…Lactylated HMGB1 is then released by macrophages, disrupting endothelial integrity, increasing vascular permeability, and contributing to endothelial cell barrier dysfunction, thereby promoting sepsis progression ( 17 ). Pyroptosis is a programmed cell death associated with inflammatory diseases, occurring in macrophages mostly ( 79 – 81 ). In non-canonical pyroptosis, NEDD4 E3 ubiquitin protein ligase (NEDD4) acts as a negative regulator of Caspase-11, and lactylated NEDD4 leads to macrophage pyroptosis ( 82 ), suggesting that lactylation might enhance inflammation by influencing pyroptosis.…”

Section: Lactylation Modulates Macrophage Activation In Lung Diseasementioning

confidence: 99%

Regulation of macrophage activation by lactylation in lung disease

Wei,

Guo,

Chen

et al. 2024

Front. Immunol.

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Lactylation is a process where lactate, a cellular metabolism byproduct, is added to proteins, altering their functions. In the realm of macrophage activation, lactylation impacts inflammatory response and immune regulation. Understanding the effects of lactylation on macrophage activation is vital in lung diseases, as abnormal activation and function are pivotal in conditions like pneumonia, pulmonary fibrosis, COPD, and lung cancer. This review explores the concept of lactylation, its regulation of macrophage activation, and recent research progress in lung diseases. It offers new insights into lung disease pathogenesis and potential therapeutic targets.

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“…2 -induced mice (52) C57BL/6J mice randomly divided into ve groups, including normal, model, bigelovin (intraperitoneal injection of 0.1 mg/kg, 1 mg/kg), and positive control group treated with nintedanib (intragastric administration of 100 mg/kg). The SiO 2 (Sigma, S5631) suspension (300 mg/kg) was injected into the trachea of mice, and the control group was injected with physiological saline.…”

Section: Biosafety Evaluationmentioning

confidence: 99%

Inhibition of NLRP3 oligomerization (active conformation) mediated by RACK1 ameliorates acute respiratory distress syndrome

Zhang,

Cui,

Yang

et al. 2024

Preprint

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Aberrant activation of the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome contributes to the pathogenesis of fatal and perplexing pulmonary diseases. Although pharmacologically inhibiting NLRP3 inflammasome brings potent therapeutic effects in several clinical trials and preclinical models, the molecular chaperones and transition detail in the formation of active oligomer from an auto-suppressed state remain controversial. Here, we showed that sesquiterpene bigelovin inhibited NLRP3 inflammasome activation and release of the downstreaming pro-inflammatory cytokines by canonical, noncanonical, and alternative pathways at nanomolar ranges. Chemoproteomic target identification disclosed that bigelovin covalently bound to the cysteine 168 of RACK1 and blocked the interaction between RACK1 and NLRP3 monomer, thereby interfering NLRP3 inflammasome oligomerization in vitro and in vivo. Treatment by bigelovin significantly alleviated the severity of NLRP3-related pulmonary disorders in murine models, such as LPS-induced ARDS and silicosis. These results consolidated the intricate role of RACK1 in transiting the NLRP3 state and provided a new anti-inflammatory lead and therapy for NLRP3-driven diseases.

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VX-765 attenuates silica-induced lung inflammatory injury and fibrosis by modulating alveolar macrophages pyroptosis in mice

Cited by 14 publications

References 32 publications

Pyroptotic cell death: an emerging therapeutic opportunity for radiotherapy

Pyroptotic cell death: an emerging therapeutic opportunity for radiotherapy

Regulation of macrophage activation by lactylation in lung disease

Inhibition of NLRP3 oligomerization (active conformation) mediated by RACK1 ameliorates acute respiratory distress syndrome

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