The proliferative effects of asbestos-exposed peripheral blood mononuclear cells on mesothelial cells

Our plain-English summary of The proliferative effects of asbestos-exposed peripheral blood mononuclear cells on mesothelial cells, by Y. Maki, Y. Nishimura, S. Toyooka, et al (Oncology Letters, 2016).

The study

• Authors: Y. Maki, Y. Nishimura, S. Toyooka, J. Soh, K. Tsukuda, K. Shien, M. Furukawa, T. Muraoka, T. Ueno, N. Tanaka, H. Yamamoto, H. Asano, M. Maeda, N. Kumagai-Takei, S. Lee, H. Matsuzaki, T. Otsuki, S. Miyoshi
• Journal: Oncology Letters
• Published: 2016;11(5):3308-3316
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma (MM) is thought to arise from the direct effect of asbestos on mesothelial cells. However, MM takes a long time to develop following exposure to asbestos, which suggests that the effects of asbestos are complex. The present study examined the effects of asbestos exposure on the cell growth of MeT-5A human mesothelial cells via cytokines produced by immune cells. Peripheral blood mononuclear cells (PBMCs) were stimulated with antibodies against cluster of differentiation (CD)3 and CD28 upon exposure to the asbestos chrysotile A (CA) or crocidolite (CR); the growth of MeT-5A cells in media supplemented with PBMC culture supernatants was subsequently examined. MeT-5A cells exhibited an increase in proliferation when grown in supernatant from the 7-day PBMC culture exposed to CA or CR. Analysis of cytokine production demonstrated increased levels of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1α, IL-1β, IL-3, IL-5, IL-13 and IL-17A in supernatants. Individual administration of these cytokines, excluding G-CSF and GM-CSF, led to an increase in cell growth of MeT-5A, whereas this effect was not observed following the combined administration of these cytokines. The results indicate that cytokines secreted by immune cells upon exposure to asbestos cause an increase in the growth activity of mesothelial cells, suggesting that alterations in the production of cytokines by immune cells may contribute to tumorigenesis in individuals exposed to asbestos.

In plain English

This was a laboratory study of cells grown in dishes; no people or animals were exposed. The authors took white blood cells (peripheral blood mononuclear cells) from three healthy donors. They stimulated the T cells with antibodies and cultured the cells for 2 or 7 days with 5 or 20 µg/ml of chrysotile A or crocidolite asbestos. This culture fluid was then added to MeT-5A, a non-malignant human pleural mesothelial cell line. Fluid from 7-day cultures with 20 µg/ml of either fiber significantly increased mesothelial cell growth. Fluid from 7-day cultures with 5 µg/ml showed a slight, non-significant tendency, and 2-day fluid did not significantly increase growth. Of 26 cytokines (immune signalling proteins) measured, the authors reported eight as significantly higher with asbestos, but in their table only five met the p less than 0.01 cutoff set in their methods. Six of the eight, added singly, significantly increased growth, though by less than the culture fluid did. Adding all of them together did not significantly increase growth. The authors concluded that cytokines from asbestos-exposed immune cells may contribute to malignant mesothelioma, alongside asbestos's direct effect.

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: Peripheral blood mononuclear cells from three healthy donors (Japan), and the non-malignant SV40-transformed human pleural mesothelial cell line MeT-5A
• Exposure: Chrysotile A or crocidolite at 5 or 20 µg/ml for 2 or 7 days, applied to immune cells stimulated with anti-CD3 and anti-CD28 antibodies. The mesothelial cells were exposed only to the resulting culture fluid or to recombinant cytokines.
• Main results:
  • MeT-5A cells given fluid from 7-day cultures significantly increased growth (optical density) at 20 µg/ml: control 1.219±0.216; chrysotile A 20 µg/ml 2.085±0.586, P<0.0001; crocidolite 20 µg/ml 1.908±0.632, P<0.0001. At 5 µg/ml: chrysotile A 1.665±0.344, P=0.026; crocidolite 1.583±0.331, P=0.028. The 5 µg/ml results were described as a slight, non-significant tendency.
  • Fluid from 2-day cultures did not significantly enhance MeT-5A growth compared with control
  • No significant differences were found between chrysotile A and crocidolite at equivalent doses and durations
  • The authors reported that 8 of 26 cytokines (G-CSF, GM-CSF, IL-1α, IL-1β, IL-3, IL-5, IL-13, IL-17A) were significantly higher in fluid from asbestos-exposed cultures than in controls. Th1 cytokines such as IFN-γ did not increase.
  • The methods set significance for cytokine measurements at P less than 0.01, while Table I marks significance at P less than 0.05. In Table I, only G-CSF, GM-CSF, IL-1β, IL-3 and IL-17A reach P less than 0.01 in any condition. IL-1α (lowest P 0.012), IL-5 (lowest P 0.014) and IL-13 (lowest P 0.011) do not.
  • Recombinant cytokines added one at a time, other than G-CSF and GM-CSF, significantly increased MeT-5A growth (P<0.01). The differences were not large.
  • When all the cytokines were added together, MeT-5A growth did not differ significantly from control (1.027±0.089 against a control of 1.000±0.035; P=0.803). In selected combinations, no increase in cell growth was observed.
• The authors' conclusion: The authors concluded that cytokines produced by immune cells exposed to asbestos may contribute to the development of malignant mesothelioma in asbestos-exposed individuals, in addition to asbestos's direct effect on mesothelial cells. They called for further studies.
• Limitations the authors state:
  • The growth increases caused by recombinant cytokines were smaller than those caused by the culture fluid from asbestos-exposed immune cells
  • The optimal combination and concentrations of cytokines for mesothelial cell growth were not identified
  • Other secretory factors, including cytokines not assayed and non-cytokine molecules, were not examined

Topics

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Malignant Mesothelioma, Asbestos Exposure, Cytokine, Chrysotile, Crocidolite, MeT-5A Cells, Macrophage.

Related studies

• Downregulation of microRNA-34 induces cell proliferation and invasion of human mesothelial cells — N. Tanaka, S. Toyooka, et al. (2013)
• Induction of CD69 antigen expression in peripheral blood mononuclear cells on exposure to silica, but not by asbestos/chrysotile-A — P. Wu, F. Hyodoh, et al. (2005)
• Man-made mineral fibers induce apoptosis of human peripheral blood mononuclear cells similarly to chrysotile B — Z. Ma, T. Otsuki, et al. (1999)
• Strong anti-tumor effect of NVP-AUY922, a novel Hsp90 inhibitor, on non-small cell lung cancer — T. Ueno, K. Tsukuda, et al. (2012)
• The degree of microRNA-34b/c methylation in serum-circulating DNA is associated with malignant pleural mesothelioma — T. Muraoka, J. Soh, et al. (2013)
• Expression of the T cell receptor Vbeta repertoire in a human T cell resistant to asbestos-induced apoptosis and peripheral blood T cells from patients with silica and asbestos-related diseases — Y. Nishimura, Y. Miura, et al. (2006)

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