The NLRP3 inflammasome in pathogenic particle and fibre-associated lung inflammation and diseases

Our plain-English summary of The NLRP3 inflammasome in pathogenic particle and fibre-associated lung inflammation and diseases, by M. Sayan, B.T. Mossman (Particle and Fibre Toxicology, 2016).

The study

• Authors: M. Sayan, B.T. Mossman
• Journal: Particle and Fibre Toxicology
• Published: 2016;13(1):51
• Type of article: Review
• Cited by: 244 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The concept of the inflammasome, a macromolecular complex sensing cell stress or danger signals and initiating inflammation, was first introduced approximately a decade ago. Priming and activation of these intracellular protein platforms trigger the maturation of pro-inflammatory chemokines and cytokines, most notably, interleukin-1β (IL-1β) and IL-18, to promulgate innate immune defenses. Although classically studied in models of gout, Type II diabetes, Alzheimer's disease, and multiple sclerosis, the importance and mechanisms of action of inflammasome priming and activation have recently been elucidated in cells of the respiratory tract where they modulate the responses to a number of inhaled pathogenic particles and fibres. Most notably, inflammasome activation appears to regulate the balance between tissue repair and inflammation after inhalation of pathogenic pollutants such as asbestos, crystalline silica (CS), and airborne particulate matter (PM). Different types of fibres and particles may have distinct mechanisms of inflammasome interaction and outcome. This review summarizes the structure and function of inflammasomes, the interplay between various chemokines and cytokines and cell types of the lung and pleura after inflammasome activation, and the events leading to the development of non-malignant (allergic airway disease and chronic obstructive pulmonary disease (COPD), asbestosis, silicosis) and malignant (mesothelioma, lung cancer) diseases by pathogenic particulates. In addition, it emphasizes the importance of communication between cells of the immune system, target cells of these diseases, and components of the extracellular matrix (ECM) in regulation of inflammasome-mediated events.

In plain English

This article was a review of earlier research, not a new study. The authors searched PubMed for papers on the NLRP3 inflammasome together with asbestos (23 citations), crystalline silica (43), airborne particulate matter (19), carbon nanotubes (15) and diesel exhaust particles (1 review). The NLRP3 inflammasome is a protein complex inside cells that senses damage and starts inflammation. The authors described how it works and summarized laboratory and animal studies linking it to asbestosis, silicosis, asthma, COPD, lung cancer and mesothelioma. Studies they cited, including the authors' own earlier work, reported that crocidolite asbestos triggered release of the inflammatory signal IL-1β through NLRP3 in human immune cells and in mice. Other cited work found that crocidolite and erionite primed and activated NLRP3 in human mesothelial cells in the laboratory. In one study, some activation measures were statistically significant only at high, toxic fibre amounts. In a cited mouse study, mice lacking an inflammasome component developed mesothelioma later and less often. The authors concluded that these diseases are associated with inflammation and NLRP3 activation. They noted that few studies test several doses or report cytotoxicity.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published laboratory, animal and other studies on the NLRP3 inflammasome and inhaled particles and fibres
• Who was studied: Published English-language literature found through PubMed searches: inflammasomes and asbestos (23 citations), silica (43), airborne particulate matter (19), carbon nanotubes (15), diesel exhaust particles (1 cited review). About one third of these citations were original reports that the authors referenced.
• Exposure: Asbestos (crocidolite, amosite, chrysotile, Libby amphibole), erionite, crystalline silica, airborne particulate matter, carbon nanotubes and diesel exhaust particles, mostly in cell culture and animal experiments
• Main results:
  • The authors' earlier cited study reported that release of IL-1β induced by crocidolite asbestos depended on the NLRP3 inflammasome. This was seen in human monocyte-derived macrophages and THP-1 cells, and after inhalation of asbestos by wild-type and NLRP3 null mice.
  • A cited study found that crocidolite asbestos and erionite, but not glass beads, primed and activated NLRP3 inflammasomes in human mesothelial cells in vitro.
  • In that mesothelial cell study, priming occurred at both non-toxic and toxic concentrations. Caspase-1 activity and release of HMGB1, IL-1β and IL-18 were statistically significant only at high, toxic amounts of fibres.
  • In a cited mouse study, mice lacking the inflammasome component Asc showed significantly delayed mesothelioma onset and reduced mesothelioma incidence compared with wild-type mice. In the same work, mice exposed to crocidolite asbestos and given anakinra (an IL-1 receptor blocker) showed a marked delay in median time of mesothelioma onset compared with mice given vehicle control.
  • Cited studies reported that long needle-like carbon nanotubes and asbestos fibres activated the NLRP3 inflammasome by similar mechanisms, unlike shorter or tangled materials or glass beads.
  • For diesel exhaust particles, cited work found that IL-1β levels were not reduced in NLRP3 or caspase-1 null mice, pointing to inflammasome-independent mechanisms.
• The authors' conclusion: The authors concluded that the references they cited show that lung cancers, mesotheliomas, asbestosis, silicosis, asthma and COPD are associated with acute or chronic inflammation and with activation of the NLRP3 inflammasome by several different particles and fibres.
• Limitations the authors state:
  • The authors noted that particle studies rarely test several concentrations and seldom report cytotoxicity, so dose-response evidence is limited.
  • The review did not focus on engineered nanomaterials other than carbon nanotubes compared with asbestos.
  • The authors stated there is no agreement on a single mechanism of NLRP3 activation.

Topics

Medical terms in this study, explained in our Lexicon: Inflammation, Cytokine, Crystalline, Pleura, COPD, Silicosis, Mesothelioma, Lung Cancer.

Related studies

• Nanoparticles activate the NLR pyrin domain containing 3 (Nlrp3) inflammasome and cause pulmonary inflammation through release of IL-1α and IL-1β — A.S. Yazdi, G. Guarda, et al. (2010)
• The Synthetic Lignan Secoisolariciresinol Diglucoside Prevents Asbestos-Induced NLRP3 Inflammasome Activation in Murine Macrophages — R.A. Pietrofesa, P. Woodruff, et al. (2017)
• The NLRP3 inflammasome is activated by nanoparticles through ATP, ADP and adenosine — L. Baron, A. Gombault, et al. (2015)
• Dose-response modeling of NLRP3 inflammasome-mediated diseases: asbestos, lung cancer, and malignant mesothelioma as examples — L.A. Cox (2019)
• Long, needle-like carbon nanotubes and asbestos activate the NLRP3 inflammasome through a similar mechanism — J. Palomäki, E. Välimäki, et al. (2011)
• Vimentin regulates activation of the NLRP3 inflammasome — G. dos Santos, M.R. Rogel, et al. (2015)

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