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Translating Basic Research into Clinical PracticeInflammasomes in Respiratory Disease: From Bench to Bedside
Section snippets
Inflammasomes: Platforms for Caspase-1 Activation
Inflammasomes are defined as intracellular multiprotein complexes that facilitate the proximity-induced autoactivation of the proinflammatory cysteine protease caspase-1. Similar to apical caspases activating the death receptor-mediated and the mitochondria-dependent apoptotic cell death pathways, caspase-1 is produced as an inactive protease zymogen that resides in the cytosol of myeloid and epithelial cells. Upon detection of endogenous or exogenous signals indicating imminent danger, sensor
Flu (Influenza A Virus)
Influenza A virus, a negative-stranded RNA virus, is a major cause of human respiratory infections and a frequent trigger of exacerbations in patients with asthma or COPD. Influenza A viruses are sensed by three different PRRs, namely the endosomal TLR7 that recognizes viral single-stranded RNA (ssRNA), the cytosolic retinoic acid-inducible gene-I receptor that senses viral ssRNA bearing 5′-triphosphates, and the NLRP3 inflammasome that activates caspase-1 in macrophages and dendritic cells.45
Asthma
A common denominator of chronic inflammatory lung diseases, such as asthma, COPD, and pulmonary fibrosis, is that they represent complex diseases that result from the interaction between genetic susceptibility and environmental exposures. Indeed, several findings suggest that the inflammasome pathway might be involved in the pathogenesis of asthma. First, genomewide association studies of asthma have shown a significant association with single-nucleotide polymorphisms within the IL18R1 gene on
Pharmacologic Targeting of Inflammasome Signaling
The inflammasome provides several promising targets for pharmacological intervention in respiratory infection and chronic lung inflammation. Modulation of inflammasome-dependent biologic outcomes may be accomplished at several levels, for instance by preventing the nuclear factor-κB-dependent upregulation of NLRP3 and the inflammasome substrates proIL-1β and proIL-18 (eg, BAY 11-7082); by inhibiting inflammasome assembly and activation by means of P2X7 antagonists, glyburide, or cytokine
Acknowledgments
Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.
Role of sponsors: There was no role for the funding bodies in writing and editing of the manuscript.
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2022, ChemosphereCitation Excerpt :Tsai et al. showed that Der f1, an allergen of Dermatophagoides farinae, causes pyroptosis in human bronchial epithelium via the activation of NLRP3 inflammasome (Tsai et al., 2017). These evidences indicate that other than the reported forms of PCD (necroptosis, pyroptosis and autophagy), the NLRP3 inflammasome-mediated pyroptosis also belongs to a major PCD type that contributes to the disease development of COPD and other forms of lung diseases (Brusselle et al., 2014; Lee et al., 2016; Pinkerton et al., 2017; Sauler et al., 2019). Emerging studies have been showing that PM2.5 can significantly induce pyroptosis in mammalian cells through multiple signaling pathways.
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2022, Journal of Molecular Biology(−)-Epicatechin ameliorates cigarette smoke-induced lung inflammation via inhibiting ROS/NLRP3 inflammasome pathway in rats with COPD
2021, Toxicology and Applied PharmacologyCitation Excerpt :Emerging data have also suggested that NLRP3 deficiency or inhibited inflammasome-dependent activation of caspase-1 or IL-1β alleviates inflammation in some inflammatory diseases (Satoh et al., 2015; Wu et al., 2018a; Dapaah-Siakwan et al., 2019). Recently, increasing clinical and experimental studies have shown that inflammasome activation induced by exogenous factors, such as smoke exposure, promotes inflammation and plays a key role in many chronic respiratory diseases, including COPD (Brusselle et al., 2014; Abderrazak et al., 2015; Hosseinian et al., 2015; Sayan and Mossman, 2016; Peng et al., 2018; Wang et al., 2018b). Since smoke exposure and the subsequent production of reactive oxygen species (ROS) is one of the upstream factors that trigger inflammation activation, suppressing intracellular oxidative stress levels might be a suitable alternative for COPD treatment.
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2020, International ImmunopharmacologyCitation Excerpt :As mentioned above, NLRP3 inflammasome activation could lead to the activation of caspase-1, which induces the increased release of mature IL-1β and IL-18 [10,36]. A similar observation was demonstrated that, active IL-1β/IL-18 affects adaptive immune cells such as Th1 and Th17 during the infection [37,38]. Concomitantly, the level of IL-1 β in BALF [39] and serum [40] of patients with asthma are higher than those of normal controls.
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Funding/Support: Work in Dr Lamkanfi's laboratory is supported in part by the European Union [Marie-Curie Grant 256432], European Research Council [Grant 281600], and the Fund for Scientific Research Flanders (FWO) [Grants G030212N, 1.2.201.10.N.00, and 1.5.122.11.N.00]. Drs Provoost and Bracke are postdoctoral researchers of FWO. Presented work within the Department of Respiratory Medicine of Ghent University is funded by grants from the FWO, the Concerted Action of Ghent University, and the Interuniversity Attraction Poles Program.
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