Cell signaling pathways elicited by asbestos

Our plain-English summary of Cell signaling pathways elicited by asbestos, by B.T. Mossman, S. Faux, Y. Janssen, et al (Environmental Health Perspectives, 1997).

The study

• Authors: B.T. Mossman, S. Faux, Y. Janssen, L.A. Jimenez, C. Timblin, C. Zanella, J. Goldberg, E. Walsh, A. Barchowsky, K. Driscoll
• Journal: Environmental Health Perspectives
• Published: 1997;105 Suppl 5(Suppl 5):1121-5
• Cited by: 42 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

In recent years, it has become apparent that minerals can trigger alterations in gene expression by initiating signaling events upstream of gene transactivation. These cascades may be initiated at the cell surface after interaction of minerals with the plasma membrane either through receptorlike mechanisms or integrins. Alternatively, signaling pathways may be stimulated by active oxygen species generated both during phagocytosis of minerals and by redox reactions on the mineral surface. At least two signaling cascades linked to activation of transcription factors, i.e., DNA-binding proteins involved in modulating gene expression and DNA replication, are stimulated after exposure of lung cells to asbestos fibers in vitro. These include nuclear factor kappa B (NF kappa B) and the mitogen-activated protein kinase (MAPK) cascade important in regulation of the transcription factor, activator protein-1 (AP-1). Both NF kappa B and AP-1 bind to specific DNA sequences within the regulatory or promoter regions of genes that are critical to cell proliferation and inflammation. Unraveling the cell signaling cascades initiated by mineral dusts and pharmacologic inhibition of these events may be important for the control and treatment of mineral-associated occupational diseases.

In plain English

This paper, based on a presentation at a 1996 scientific meeting, described laboratory experiments on animal cells grown in dishes, not studies of people. It drew partly on the authors' own earlier published work. Hamster tracheal (windpipe) epithelial cells were exposed to crocidolite asbestos at 1.25 or 5.0 micrograms per square centimeter of dish. Crocidolite increased protein complexes, identified as p65/p50 and p50, that bind to the DNA site of NF-kappa-B, a protein that switches genes on. The increase was statistically significant (p less than 0.05) only for p65/p50. Adding N-acetylcysteine, an antioxidant-related agent, lessened these changes. In rat pleural mesothelial cells, crocidolite-induced activation of the ERK signaling pathway was blocked by agents acting on the epidermal growth factor receptor. In rat alveolar type II lung cells, preliminary data showed crocidolite stimulated the ERK pathway, not JNK, at a concentration that caused apoptosis (cell death) but not cell growth. The authors concluded that mineral dusts may stimulate multiple cell-signaling pathways, with oxidants as probable mediators, and that drugs blocking these pathways might be feasible for controlling cell outcomes.

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: Laboratory (in vitro) cell-culture study presented at a scientific meeting, partly summarizing the authors' own earlier published experiments
• Who was studied: A diploid line of hamster tracheal epithelial (HTE) cells, used at passages 38 to 48; related work also used rat pleural mesothelial (RPM) cells and rat alveolar type II epithelial (RLE) cells. No human subjects.
• Exposure: Processed crocidolite asbestos (NIEHS preparation) added to culture medium at 1.25 or 5.0 micrograms per square centimeter of dish, examined from 2 to 24 hours; nonfibrous analogs used as negative controls
• Main results:
  • In HTE cells, crocidolite increased p65/p50 and p50 protein complexes binding to the NF-kappa-B DNA sequence compared with sham controls
  • Although both complexes showed similar upward trends in HTE cells, statistically significant increases (p less than 0.05) were seen only for p65/p50
  • In HTE cells, these increases were lessened when N-acetylcysteine (NAC) was added beforehand, which the authors said suggests oxidative stress may be important
  • In RPM cells, crocidolite-induced ERK1/ERK2 phosphorylation and ERK2 kinase activity were blocked by suramin or by AG 1478, which inhibits the epidermal growth factor receptor (from the authors' earlier work)
  • In RLE cells (preliminary data), crocidolite at 5 micrograms per square centimeter caused apoptosis but not cell proliferation, selectively stimulated the ERK pathway, and did not increase JNK activity
  • In RPM cells, an MEK1,2 inhibitor that blocks ERK activation inhibited asbestos-induced apoptosis (cited from the authors' work in press)
• The authors' conclusion: The authors concluded that multiple cell-signaling pathways may be stimulated by mineral dusts, probably mediated by oxidants, and that using drugs to manipulate parts of the MAPK cascade may be feasible for controlling outcomes of asbestos exposure in respiratory tract cells
• Limitations the authors state:
  • The authors described the findings linking ERK and JNK activation to apoptosis and proliferation in RLE cells as preliminary

Topics

The National Library of Medicine indexes this study under subjects our site covers: Crocidolite.

Medical terms in this study, explained in our Lexicon: Phagocytosis, Nuclear Factor kappa B (NF-κB), Inflammation, Occupational Disease.

Related studies

• Asbestos-induced activation of cell signaling pathways in human bronchial epithelial cells — X. Wang, J.M. Samet, et al. (2006)
• Oxidants and signaling by mitogen-activated protein kinases in lung epithelium — B.T. Mossman, K.M. Lounsbury, et al. (2006)
• AKT/mTOR and c-Jun N-terminal kinase signaling pathways are required for chrysotile asbestos-induced autophagy — Z. Lin, T. Liu, et al. (2014)
• Merlin, a "magic" linker between extracellular cues and intracellular signaling pathways that regulate cell motility, proliferation, and survival — I. Stamenkovic, Q. Yu (2010)
• The c-Jun N-terminal kinase signaling pathway mediates chrysotile asbestos-induced alveolar epithelial cell apoptosis — P. Li, T. Liu, et al. (2015)
• Epithelial-mesenchymal transition involved in pulmonary fibrosis induced by multi-walled carbon nanotubes via TGF-beta/Smad signaling pathway — T. Chen, H. Nie, et al. (2014)

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