Nuclear Factor Kappa-B Activation by Particles and Fibers

Our plain-English summary of Nuclear Factor Kappa-B Activation by Particles and Fibers, by R.P. Schins, K. Donaldson (Inhalation Toxicology, 2000).

The study

• Authors: R.P. Schins, K. Donaldson
• Journal: Inhalation Toxicology
• Published: 2000;12 Suppl 3:317-26
• Cited by: 34 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

In recent years, particle research has focused on activation pathways of transcription factors that are known to regulate genes whose abnormal expression is associated with the pathogenesis of particle-associated lung disorders such as fibrosis, cancer, COPD, and asthma. This article reviews the effects of different particles and fibers on the transcriptional activation of nuclear factor kappa-B (NF-kB), which is involved in the activation of a variety of proinflammatory genes. Particulates that have been found to activate NF-κB, include asbestos, man-made fibers, quartz, and ambient particulates, such as residual oil fly ashes (ROFA) and diesel exhaust particles (DEP). In line with this, a number of NF-κB-regulated genes have been found to be upregulated, such as tumour necrosis factor-alpha (TNFα), macrophage inflammatory protein-2 (MIP-2), the interleukins IL-6 and IL-8, cyclooxygenase- II (COX-II), and inducible nitric oxide synthase (iNOS). Important mechanisms involved in the activation of NF-kB by particles or fibers include a role for reactive oxygen species, arachidonic acid metabolism, and particle- or fiber-specific physiochemical properties (e.g., transition metals, fiber dimensions) in processes such as lipid peroxidation and (frustrated) phagocytosis. Intracellularly, NF-κB may be activated via several pathways, for example, involving protein kinase C, tyrosine kinase, or calpain. Future research on NF-κB activation by particles or fibers should aim to further identify these and other pathways and to determine the in vivo significance of this activation in the pathogenesis of lung disease.

In plain English

This article was a review, not a new study. The authors summarized published laboratory research, mostly on cells grown in dishes plus one set of rat inhalation experiments, on whether particles and fibers switch on NF-kappa B. NF-kappa B is a protein that turns on genes involved in inflammation. The reviewed studies reported activation by crocidolite, chrysotile and amosite asbestos, by some man-made fibers, by quartz, and by air pollution particles such as diesel exhaust particles. In the studies cited, riebeckite (the nonfibrous form of crocidolite), glass beads and carbon black did not activate it. In one rat study, crocidolite and chrysotile caused activation in airway lining and lung tissue 5 and 20 days after inhalation. The reviewed work pointed to roles for reactive oxygen species, iron and fiber length. The authors also described their own cell work comparing quartz with titanium dioxide. The authors concluded that how particles and fibers activate NF-kappa B is not yet fully understood. They said animal studies and analysis of human samples are needed to judge its role in human lung disease.

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: Review of published laboratory (cell culture and animal) studies
• Who was studied: Published studies, listed in the article's Table 1, testing various cell types (hamster, rat, human, mouse and porcine cells, including rat pleural mesothelial cells) and, in one case, rats exposed by inhalation
• Exposure: Asbestos (crocidolite, chrysotile, amosite); riebeckite; man-made fibers (refractory ceramic fibers RCF-1 and RCF-4, silicon carbide, MMVF10, glass fibers C100/475 and JM-100); quartz; glass beads; ambient particles (total suspended particulates, residual oil fly ash, diesel exhaust particles); carbon black; titanium dioxide
• Main results:
  • A cited study (Janssen et al., 1995) reported a dose-dependent increase in NF-kappa B activity in hamster tracheal epithelial cells treated with crocidolite
  • In a cited rat inhalation study (Janssen et al., 1997), crocidolite and chrysotile caused NF-kappa B (p65) to move into the cell nucleus in airway epithelium and interstitium at 5 and 20 days after inhalation
  • Riebeckite, the nonfibrous analogue of crocidolite, and glass beads failed to activate NF-kappa B in the cited study
  • In a cited study of human A549 lung cells (Brown et al., 1999), fibers the authors call pathogenic (amosite, RCF1, silicon carbide) produced dose-dependent NF-kappa B activation. Fibers called nonpathogenic (RCF-4, glass fiber C100/475, MMVF10) did not.
  • A cited study reported NF-kappa B activation by chrysotile and crocidolite in porcine aortic endothelial cells
  • Diesel exhaust particles activated NF-kappa B in human bronchial cells, but carbon black did not (Baeza-Squiban et al., 1999)
  • The antioxidant N-acetyl-L-cysteine was found to reduce NF-kappa B activation in hamster tracheal epithelial cells treated with asbestos
  • The iron chelator desferoxamine reduced NF-kappa B activation in cited studies, including in mouse macrophage cells treated with quartz or asbestos
  • In macrophages, longer glass fibers (17, unit garbled in the scan) caused stronger NF-kappa B activation than shorter (7) fibers (Ye et al., 1999)
  • In the authors' own earlier work on A549 cells, quartz and titanium dioxide caused similar breakdown of the inhibitor protein IkappaB-alpha, but differed in its restoration and in associated IL-8 production
• The authors' conclusion: The authors concluded that a number of particles and fibers have been reported to activate NF-kappa B, but that it is not yet fully understood how this happens or whether all pathogenic fibers and particles share common mechanisms. They said animal studies and analysis of human samples are needed to determine its significance in human lung disease.
• Limitations the authors state:
  • The only in vivo data showing persistent NF-kappa B activation came from rat inhalation experiments with asbestos from one laboratory
  • Few studies had addressed how NF-kappa B interacts with other transcription factors in response to particles or fibers
  • The role of NF-kappa B in human disease had not been determined. The authors said analysis of human samples is needed.

Topics

Medical terms in this study, explained in our Lexicon: Fibrosis, COPD, Necrosis, Macrophage, Interleukins, Inducible Nitric Oxide Synthase (iNOS), Reactive Oxygen Species (ROS), Fiber Dimensions.

Related studies

• Asbestos induces nuclear factor kappa B (NF-kappa B) DNA-binding activity and NF-kappa B-dependent gene expression in tracheal epithelial cells — Y.M. Janssen, A. Barchowsky, et al. (1995)
• Production of reactive oxygen intermediates by human macrophages exposed to soot particles and asbestos fibers and increase in NF-kappa B p50/p105 mRNA — R. Oettinger, K. Drumm, et al. (1999)
• Free radical activity of industrial fibers: role of iron in oxidative stress and activation of transcription factors — P.S. Gilmour, D.M. Brown, et al. (1997)
• Activation of alveolar macrophages and peripheral red blood cells in rats exposed to fibers/particles — F. Afaq, P. Abidi, et al. (1998)
• Asbestos fibers and silica particles stimulate rat alveolar macrophages to release tumor necrosis factor. Autoregulatory role of leukotriene B4 — C.M. Dubois, E. Bissonnette, et al. (1989)
• Pulmonary macrophages are attracted to inhaled particles through complement activation — D.B. Warheit, L.H. Overby, et al. (1988)

Browse more research in Inhalation Toxicology, or return to medical research.