Related Experiment Video
Updated: Mar 22, 2026
Generation and Expansion of Primary, Malignant Pleural Mesothelioma Tumor Lines
Published on: April 21, 2022
The proliferative effects of asbestos-exposed peripheral blood mononuclear cells on mesothelial cells
Yuho Maki1, Yasumitsu Nishimura2, Shinichi Toyooka1
1Department of General Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
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.
Insights
Asbestos exposure stimulates immune cells to release cytokines, which then increase the growth of human mesothelial cells. This suggests immune cell cytokine alterations may contribute to asbestos-related mesothelioma development.
Area of Science:
- Oncology
- Immunology
- Cell Biology
Background:
- Malignant mesothelioma (MM) development after asbestos exposure is a lengthy process, indicating complex underlying mechanisms.
- The direct impact of asbestos on mesothelial cells may not fully explain MM pathogenesis.
Purpose of the Study:
- To investigate the role of immune cell-derived cytokines in mediating asbestos's effect on mesothelial cell growth.
- To explore the relationship between asbestos exposure, immune responses, and mesothelial cell proliferation.
Main Methods:
- Peripheral blood mononuclear cells (PBMCs) were stimulated with anti-CD3/CD28 antibodies following exposure to chrysotile A (CA) or crocidolite (CR) asbestos.
- MeT-5A human mesothelial cells were cultured in media containing supernatants from stimulated PBMC cultures.
- Cytokine levels in supernatants were analyzed, and individual/combined cytokines were administered to MeT-5A cells.
Main Results:
- MeT-5A cell proliferation increased when cultured in supernatants from PBMCs exposed to CA or CR asbestos.
- Elevated levels of specific cytokines, including IL-1α, IL-1β, IL-3, IL-5, IL-13, and IL-17A, were observed.
- Individual administration of these cytokines (excluding G-CSF and GM-CSF) enhanced MeT-5A cell growth, but combined administration did not.
Conclusions:
- Cytokines secreted by immune cells in response to asbestos exposure promote mesothelial cell growth.
- Altered cytokine production by immune cells may play a significant role in the tumorigenesis of asbestos-exposed individuals.
- This study highlights the indirect role of asbestos in MM development via immune system modulation.
