Skip to main content
SpringerLink
Log in

Inflammatory Cytokines Contribute to Asbestos-Induced Injury of Mesothelial Cells

  • Published:
Lung Aims and scope Submit manuscript

Abstract

Background

Several diseases have been related to asbestos exposure, including the pleural tumor mesothelioma. The mechanism of pleural injury by asbestos fibers is not yet fully understood. The inflammatory response with release of mediators leading to a dysregulation of apoptosis may play a pivotal role in the pathophysiology of asbestos-induced pleural disease.

Objective

To determine whether pro-inflammatory cytokines produced by asbestos-exposed pleural mesothelial cells modify the injury induced by the asbestos.

Methods

Mouse pleural mesothelial cells (PMC) were exposed to crocidolite or chrysotile asbestos fibers (3.0 μg/cm2) for 4, 24, or 48 h and assessed for viability, necrosis and apoptosis, and the production of cytokines IL-1β, IL-6 and macrophage inflammatory protein-2 (MIP-2). Cells exposed to fibers were also treated with antibodies anti-IL-1β, anti-IL-6, anti- IL-1β+anti-IL-6 or anti-MIP-2 or their irrelevant isotypes, and assessed for apoptosis and necrosis. Non-exposed cells and cells treated with wollastonite, an inert particle, were used as controls.

Results

Mesothelial cells exposed to either crocidolite or chrysotile underwent both apoptosis and necrosis and released cytokines IL-1β, IL-6 and MIP-2. In the crocidolite group, apoptosis and the levels of all cytokines were higher than in the chrysotile group, at comparable concentrations. Neutralization of IL-1β andIL-6, but not MIP-2, inhibited apoptosis and necrosis, especially in the cells exposed to crocidolite fibers.

Conclusions

Both crocidolite and chrysotile asbestos fibers induced apoptosis and produced an acute inflammatory response characterized by elevated levels of IL-1β, IL-6 and MIP-2 in cultured mouse PMC. IL-1β and IL-6, but not MIP-2, were shown to contribute to asbestos-induced injury, especially in the crocidolite group.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Dusinska M, Collins A, Kazimirova A et al (2004) Genotoxic effects of asbestos in humans. Mutat Res 553:91–102

    Article  CAS  PubMed  Google Scholar 

  2. Boutin C, Dumortier P, Rey F et al (1996) Black spots concentrate oncogenic asbestos fibers in the parietal pleura. Thoracoscopic and mineralogic study. Am J Respir Crit Care Med 153:444–449

    Article  CAS  PubMed  Google Scholar 

  3. Jaurand MC, Fleury-Feith J (2005) Pathogenesis of malignant pleural mesothelioma. Respirology 10:2–8

    Article  PubMed  Google Scholar 

  4. Mutsaers SE (2002) Mesothelial cells: their structure, function and role in serosal repair. Respirology 7:171–191

    Article  PubMed  Google Scholar 

  5. Driscoll KE, Maurer JK, Higgins J et al (1995) Alveolar macrophage cytokine and growth factor production in a rat model of crocidolite-induced pulmonary inflammation and fibrosis. J Toxicol Environ Health 46:155–169

    Article  CAS  PubMed  Google Scholar 

  6. Driscoll KE (2000) TNFα and MIP-2: role in particle-induced inflammation and regulation by oxidative stress. Toxicol Lett 112–113:177–198

    Article  PubMed  Google Scholar 

  7. Bielefeldt-Ohmann H, Fitzpatrick DR, Marzo AL et al (1994) Patho- and immunobiology of malignant mesothelioma: characterisation of tumor infiltrating leucocytes and cytokine production in a murine model. Cancer Immunol Immunother 39:347–359

    Article  CAS  PubMed  Google Scholar 

  8. Broaddus VC, Yang L, Scavo LM et al (1996) Asbestos induces apoptosis of human and rabbit pleural mesothelial cells via reactive oxygen species. J Clin Invest 98:2050–2059

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Liu W, Ernst JD, Broaddus VC (2000) Phagocytosis of crocidolite asbestos induces oxidative stress, DNA damage, and apoptosis in mesothelial cells. Am J Respir Cell Mol Biol 23:371–378

    Article  CAS  PubMed  Google Scholar 

  10. Marchi E, Liu W, Broaddus VC (2000) Mesothelial cell apoptosis is confirmed in vivo by morphological change in cytokeratin distribution. Am J Physiol Lung Cell Mol Physiol 278:L528–L535

    CAS  PubMed  Google Scholar 

  11. Mossman BT, Churg A (1998) Mechanisms in the pathogenesis of asbestosis and silicosis. Am J Respir Crit Care Med 157:1666–1680

    Article  CAS  PubMed  Google Scholar 

  12. Manning CB, Vallyathan V, Mossman BT (2002) Diseases caused by asbestos: mechanisms of injury and disease development. Int Immunopharmacol 2:191–200

    Article  CAS  PubMed  Google Scholar 

  13. Broaddus VC, Everitt JI, Black B et al (2011) Non neoplastic and neoplastic pleural endpoints following fiber exposure. J Toxicol Environ Health 14:153–178

    Article  CAS  Google Scholar 

  14. Ramos-Nino ME, Testa JR, Altomare DA et al (2006) Cellular and molecular parameters of mesothelioma. J Cell Biochem 98:723–734

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Broaddus VC (1997) Asbestos, the mesothelial cell and malignancy: a matter of life or death. Am J Respir Cell Mol Biol 17:657–659

    Article  CAS  PubMed  Google Scholar 

Download references

Financial Support

Research Support Foundation for the State of São Paulo (FAPESP), Brazil.

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Pleura Laboratory, Pulmonary Division - Heart Institute (InCor), University of São Paulo Medical School, Rua Dr. Eneas Carvalho Aguiar 44, 10 andar, Cerqueira Cesar, São Paulo, 05403-000, Brazil

    Milena Marques Pagliarelli Acencio, Barbara Soares, Evaldo Marchi, Carlos Sergio Rocha Silva & Lisete Ribeiro Teixeira

  2. Medical College of Jundiai, São Paulo, Brazil

    Evaldo Marchi

  3. Lung Biology Center, UCSF, San Francisco, CA, USA

    V. C. Broaddus

Authors
  1. Milena Marques Pagliarelli Acencio
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Barbara Soares
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Evaldo Marchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Carlos Sergio Rocha Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lisete Ribeiro Teixeira
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. V. C. Broaddus
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Milena Marques Pagliarelli Acencio.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Acencio, M.M.P., Soares, B., Marchi, E. et al. Inflammatory Cytokines Contribute to Asbestos-Induced Injury of Mesothelial Cells. Lung 193, 831–837 (2015). https://doi.org/10.1007/s00408-015-9744-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00408-015-9744-4

Keywords

Search

Navigation