Asbestos induces tissue factor in Beas-2B cells via PI3 kinase-PKC-mediated signaling

Our plain-English summary of Asbestos induces tissue factor in Beas-2B cells via PI3 kinase-PKC-mediated signaling, by A. Iakhiaev, S. Idell (Journal of Toxicology and Environmental Health. Part a, 2004).

The study

• Authors: A. Iakhiaev, S. Idell
• Journal: Journal of Toxicology and Environmental Health. Part a
• Published: 2004;67(19):1537-47
• Read it: PubMed · Publisher

Abstract

Treatment of Beas-2B airway epithelial cells with crocidolite asbestos induced tissue factor (TF) mRNA and TF-dependent procoagulant activity. The mitogen-activated protein kinase (MAPK) inhibitors UO126 and SB203850 decreased TF expression in both naive and crocidolite-treated Beas-2B cells to the same extent. Calphostin, an inhibitor of classical and novel protein kinase C (PKC) isotypes, reduced TF mRNA in both intact and crocidolite-treated Beas-2B cells by about 50%. Conversely, the phosphatidylinositol 3-kinase (PI3 kinase) inhibitor LY294002 and a selective PKCzeta inhibitory peptide decreased TF mRNA expression in asbestos-treated cells to a greater extent than in naive cells, suggesting that signaling via this pathway contributes to asbestos-induced TF expression. These results demonstrate that crocidolite asbestos induces TF expression by Beas-2B cells and suggest that the process involves the PI3 kinase-PKCzeta signaling pathway, representing a newly recognized potential mechanism by which asbestos may contribute to lung remodeling.

In plain English

This was a laboratory study of human cells grown in dishes. The authors exposed Beas-2B human airway (bronchial) epithelial cells to crocidolite asbestos fibers (2 to 10 micrometers long) at 10 micrograms per square centimeter, a dose at which the authors' tests showed no toxicity. They measured tissue factor, a protein involved in blood clotting. Crocidolite significantly increased tissue factor protein and its clotting-related activity. A rise in tissue factor messenger RNA was reliably detectable after 18 hours. Human pleural mesothelial cells (Met-5A) treated the same way showed no appreciable change. Chemical blockers of MAP kinase pathways, and the PKC blocker calphostin, reduced tissue factor RNA about equally in treated and untreated cells. A PI3 kinase blocker reduced it by 63% in crocidolite-treated cells and 49% in untreated cells, a difference that was not statistically significant. Staurosporine and a PKC zeta blocker reduced it by 72% and 66% in treated cells, compared with 40% and 33% in untreated cells. The authors concluded this may be a newly recognized way asbestos influences airway or alveolar remodeling.

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 experiment
• Who was studied: Beas-2B human bronchial (airway) epithelial cell line; Met-5A human pleural mesothelial cells were treated the same way in selected analyses
• Exposure: crocidolite asbestos from NIEHS, fiber length 2 to 10 micrometers, heat-treated to exclude endotoxin, applied at 10 micrograms per square centimeter, mostly for 18 hours, with or without signaling inhibitors
• Main results:
  • At 10 micrograms per square centimeter, crocidolite did not induce cytotoxic effects in Beas-2B cells by the measures used: chromium-51 release, trypan blue exclusion, cell morphology and growth rates were unaffected (data not shown).
  • Tissue factor protein and tissue factor-mediated factor X activating activity were present in unstimulated Beas-2B cells and were significantly increased by crocidolite.
  • No increase in tissue factor mRNA was detectable before 18 hours; the increase was reliably detectable after 18 hours of crocidolite exposure.
  • Met-5A human pleural mesothelial cells treated with crocidolite showed no appreciable change in tissue factor mRNA or protein (data not shown).
  • No increases were detected in the phosphorylated (activated) forms of the signaling kinases measured in crocidolite-exposed Beas-2B cells.
  • The PKC inhibitor calphostin, which inhibits classical and novel PKC isotypes, reduced tissue factor mRNA by about 50% in both control and crocidolite-treated cells.
  • The p38 MAPK inhibitor SB203580 and the ERK1/2 inhibitor U0126 reduced tissue factor mRNA by about 15% and 45% respectively, in both control and asbestos-treated cells.
  • The GSK3-beta inhibitor LiCl reduced tissue factor mRNA to the same extent in untreated and crocidolite-treated cells.
  • The PI3 kinase inhibitor LY294002 reduced tissue factor mRNA by a mean 63% in crocidolite-treated cells and 49% in control cells. The difference was not statistically significant.
  • Staurosporine and a PKC zeta inhibitory peptide reduced tissue factor mRNA by 40% and 33% in control cells, and by 72% and 66% in crocidolite-treated cells.
• The authors' conclusion: The authors concluded that crocidolite's effect on lung epithelial cells represents a newly recognized pathway that may influence airway or alveolar remodeling in asbestos-induced lung injury.
• Limitations the authors state:
  • The greater inhibition by the PI3 kinase inhibitor in crocidolite-treated cells did not reach statistical significance, although the authors report it was reproducible.
  • The authors did not investigate whether the faster rise in tissue factor activity came from activation of tissue factor already present in the cells.
  • Signaling was analyzed at 18 hours even though tissue factor protein and mRNA were still accumulating at that time.

Topics

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

Medical terms in this study, explained in our Lexicon: Crocidolite.

Related studies

• Asbestos induces tissue factor in Beas-2B human lung bronchial epithelial cells in vitro — A. Iakhiaev, U. Pendurthi, et al. (2004)
• Activation of p38 MAP kinase by asbestos in rat mesothelial cells is mediated by oxidative stress — W.A. Swain, K.J. O'Byrne, et al. (2004)
• Cell signaling and transcription factor activation by asbestos in lung injury and disease — A. Shukla, M. Ramos-Nino, et al. (2003)
• Involvement of protein kinase C, phospholipase C, and protein tyrosine kinase pathways in oxygen radical generation by asbestos-stimulated alveolar macrophage — Y. Lim, S.H. Kim, et al. (1997)
• The duration of nuclear extracellular signal-regulated kinase 1 and 2 signaling during cell cycle reentry distinguishes proliferation from apoptosis in response to asbestos — Z. Yuan, D.J. Taatjes, et al. (2004)
• Asbestos-induced activation of cell signaling pathways in human bronchial epithelial cells — X. Wang, J.M. Samet, et al. (2006)

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