Inflammatory Alteration of Human T Cells Exposed Continuously to Asbestos.

Naoko Kumagai-Takei,Nagisa Sada,Megumi Maeda,Min Yu,Kei Yoshitome,Yasumitsu Nishimura,Shoko Yamamoto,Suni Lee,Takemi Otsuki,Hidenori Masuzzaki

doi:10.3390/ijms19020504

Abstract

Asbestos is a known carcinogen and exposure can lead to lung cancer and malignant mesothelioma. To examine the effects of asbestos fibers on human immune cells, the human T cell leukemia/lymphoma virus (HTLV)-1 immortalized human T cell line MT-2 was employed. Following continuous exposure to asbestos fibers for more than eight months, MT-2 sublines showed acquisition of resistance to asbestos-induced apoptosis with decreased death signals and increased surviving signals. These sublines showed various characteristics that suggested a reduction in anti-tumor immunity. On the other hand, inflammatory changes such as expression of MMP7, CXCR5, CXCL13 and CD44 was found to be markedly higher in sublines continuously exposed to asbestos compared with original MT-2 cells. All of these molecules contribute to lung inflammation, T and B cell interactions and connections between mesothelial cells and T cells. Thus, further investigation focusing on these molecules may shed light on the role of chronic inflammation caused by asbestos exposure and the occurrence of malignant mesothelioma. Finally, regarding peripheral T cells from healthy donors (HD) and asbestos-exposed patients with pleural plaque (PP) or malignant pleural mesothelioma (MPM), following stimulation of CD4+ T cells, T cells from MPM patients showed reduced potential of interferon (IFN)-γ expression. Moreover, levels of interleukin (IL)-6, one of the most important cytokines in chronic inflammation, in cultured supernatants were higher in PP and MPM patients compared with HD. Overall, asbestos-induced chronic inflammation in the lung as well as the pleural cavity may facilitate the onset of asbestos-induced cancers due to alterations in the interactions among fibers, immune cells such as T and B cells and macrophages, and mesothelial and lung epithelial cells. Further investigations regarding chronic inflammation caused by asbestos fibers may assist in identifying molecular targets for preventive and therapeutic strategies related to the effects of asbestos exposure.

Highlights

Asbestos is known to cause various benign and malignant pulmonary diseases [1,2]
The effects of continuous asbestos exposure on human T cells using the MT-2 cell line as well as findings using peripheral blood CD4+ T cells were introduced from the viewpoint of inflammation
Asbestos-induced cancers such as lung cancer and mesothelioma may be derived from chronic inflammation caused by asbestos exposure and altered interactions among various immune cells such as macrophages, T cells including effector T cells, regulatory T and Th17 cells, B cells, and others

Summary

Introduction

Asbestos is known to cause various benign and malignant pulmonary diseases [1,2]. Non-cancerous disease such as asbestosis is defined as progressive pulmonary fibrosis with many patients suffering from shortness of breath, coughing, wheezing and chest pain [3,4]. From the viewpoint of the long-lasting effects of asbestos remaining in the pulmonary spaces and the persistent interactions among asbestos fibers and immune cells, increased expression of CXCL13 may contribute to the formation of chronic inflammation in the lung and the occurrence of fibrosis, as well as cancerous changes in lung epithelial and mesothelial cells.

Results

Conclusion