The Inflammasome NLR Family Pyrin Domain-Containing Protein 3 (NLRP3) as a Novel Therapeutic Target for Idiopathic Pulmonary Fibrosis

Biancatelli, Ruben Manuel Luciano Colunga; Solopov, Pavel; Catravas, John D.

doi:10.1016/j.ajpath.2022.03.003

Cited by 23 publications

(15 citation statements)

References 103 publications

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“…The NLR family, pyrin domain-containing 3 (NLRP3) protein is an intracellular signaling molecule that recognizes a wide range of pathogens, environmental factors, and host-derived factors, including ATP [ 10 ]. The NLRP3 inflammasome consists of the NLRP3, the ASC adaptor, and caspase-1, which is activated by various danger signals [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

The Effects of Curcumin on Inflammasome: Latest Update

et al. 2023

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Curcumin, a traditional Chinese medicine extracted from natural plant rhizomes, has become a candidate drug for the treatment of different diseases due to its anti-inflammatory, anticancer, antioxidant, and antibacterial activities. Curcumin is generally beneficial to improve human health with anti-inflammatory and antioxidative properties as well as antitumor and immunoregulatory properties. Inflammasomes are NLR family, pyrin domain-containing 3 (NLRP3) proteins that are activated in response to a variety of stress signals and that promote the proteolytic conversion of pro-interleukin-1β and pro-interleukin-18 into active forms, which are central mediators of the inflammatory response; inflammasomes can also induce pyroptosis, a type of cell death. The NLRP3 protein is involved in a variety of inflammatory pathologies, including neurological and autoimmune disorders, lung diseases, atherosclerosis, myocardial infarction, and many others. Different functional foods may have preventive and therapeutic effects in a wide range of pathologies in which inflammasome proteins are activated. In this review, we have focused on curcumin and evidenced its therapeutic potential in inflammatory diseases such as neurodegenerative diseases, respiratory diseases, and arthritis by acting on the inflammasome.

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Section: Introductionmentioning

confidence: 99%

The Effects of Curcumin on Inflammasome: Latest Update

et al. 2023

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“…Registries of patients with IPF with extended follow-up are necessary to evaluate the effectiveness and safety of these IPF treatments in the real-world setting, and could assist in the design of future studies with new experimental drugs for IPF (such as pamrevlumab, pentraxin-2, autotaxin inhibitors, galectin-3 inhibitors, phosphodiesterase 4 inhibitors, HSP90 inhibitors, NLRP3 inhibitors, etc.) [ 38 , 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

Russian Registry of Idiopathic Pulmonary Fibrosis: Clinical Features, Treatment Management, and Outcomes

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Merzhoeva

et al. 2023

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A registry of patients with idiopathic pulmonary fibrosis (IPF) was founded in Russia in 2016. The aim of this study was to analyze the demographic, clinical, functional, radiological, and morphological data of the patients included in this registry. Methods. This was a prospective multicenter, observational, non-interventional study. Patients’ risk factors, demographics, clinical data, results of high-resolution computed tomography (HRCT) of the chest and pulmonary function testing, and lung tissue biopsy findings were analyzed. We also analyzed the exercise tolerance (6-min walking test) of patients, serological markers of systemic connective tissue diseases, treatment, clinical course, and outcomes of the disease. Multidisciplinary discussion (MDD) was used as needed. Results. One thousand three hundred and fifty-three patients were included in the registry from 2016 to 2020. The mean age was 64.4 ± 10.7 years, most patients were active smokers or ex-smokers. Antifibrotic therapy was administered to 90 of 948 patients (9.5%). Since starting the registry in 2016, the incidences of IPF have increased and the time period from manifestation of the disease to making the diagnosis has shortened, the number of patients on antifibrotic therapy has increased and the number of patients taking systemic steroids decreased. Conclusion. The registry of patients with IPF was helpful to improve IPF diagnosis and to implement antifibrotic agents in clinical practice. Further analysis of the clinical course and prognostic markers of IPF in the Russian population is needed. An analysis of the long-term efficacy of antifibrotic therapy in this population is also important.

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“…The involvement of pro-inflammatory pathways in the development of PF has also been demonstrated in various mouse models ( Izbicki et al, 2002 ; Marinova et al, 2019 ; Solopov et al, 2020 ). Several publications further suggest that the NLRP3 inflammasome plays an important role in fibrogenesis ( Ma et al, 2020 ; Ranta-aho et al, 2021 ; Colunga Biancatelli et al, 2022b ). Here, we analyzed the leucocyte and total protein contents in bronchoalveolar lavage, the expression of the pro-inflammatory and pro-fibrotic cytokine, TGF-β, and of NLRP3 inflammasome, which designate inflammation of alveoli, migration of immune cell, and alveolar-capillary hyper-permeability.…”

Section: Discussionmentioning

confidence: 99%

Optimizing antidotal treatment with the oral HSP90 inhibitor TAS-116 against hydrochloric acid-induced pulmonary fibrosis in mice

et al. 2022

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Exposure to high concentrations of hydrochloric acid (HCl) can lead to severe acute and chronic lung injury. In the aftermath of accidental spills, victims may be treated for the acute symptoms, but the chronic injury is often overlooked. We have developed a mouse model of acute and chronic lung injury, in which the peak of acute lung injury occurs on the day 4 after HCl exposure. We have also demonstrated that HSP90 inhibitors are effective antidotes when administered starting 24 h after HCl. In this study we examined the hypothesis that the novel oral HSP90 inhibitor TAS-116 can effectively ameliorate HCl-induced lung injury even when treatment starts at the peak of the acute injury, as late as 96 h after HCl. C57BI/6J mice were intratracheally instilled with 0.1N HCl. After 24 or 96 h, TAS-116 treatment began (3.5, 7 or 14 mg/kg, 5 times per week, p. o.) for either 2,3 or 4 or weeks. TAS-116 moderated the HCl-induced alveolar inflammation, as reflected in the reduction of white blood cells and total protein content in bronchoalveolar lavage fluid (BALF), overexpression of NLRP3 inflammasome, and inhibited the activation of pro-fibrotic pathways. Furthermore, TAS-116 normalized lung mechanics and decreased the deposition of extracellular matrix proteins in the lungs of mice exposed to HCl. Delayed and shortened treatment with TAS-116, successfully blocked the adverse chronic effects associated with acute exposure to HCl.

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The Inflammasome NLR Family Pyrin Domain-Containing Protein 3 (NLRP3) as a Novel Therapeutic Target for Idiopathic Pulmonary Fibrosis

Cited by 23 publications

References 103 publications

The Effects of Curcumin on Inflammasome: Latest Update

The Effects of Curcumin on Inflammasome: Latest Update

Russian Registry of Idiopathic Pulmonary Fibrosis: Clinical Features, Treatment Management, and Outcomes

Optimizing antidotal treatment with the oral HSP90 inhibitor TAS-116 against hydrochloric acid-induced pulmonary fibrosis in mice

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