Journal
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
Volume 45, Issue 3, Pages 470-479Publisher
AMER THORACIC SOC
DOI: 10.1165/rcmb.2010-0213OC
Keywords
asbestos; malignant mesothelioma; CXCR3; IFN-gamma
Funding
- Special Coordination Funds for Promoting Science and Technology [H18-1-3-3-1]
- Ministry of Education, Culture, Sports, Science and Technology of Japan [18390186, 19659153, 19790411, 20390178, 22700933]
- Kawasaki Medical School [18-209T, 19-205Y, 20-210O]
- Grants-in-Aid for Scientific Research [19659153, 19790411, 22700933, 23790387, 20390178, 18390186] Funding Source: KAKEN
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Because patients with silicosis who are chronically exposed to silica particles develop not only pulmonary fibrosis, but also complications involving autoimmune diseases such as rheumatoid arthritis and systemic sclerosis, exposure to asbestos may affect the human immune system. This immunologic effect may impair antitumor immune function because cancer complications such as lung cancer and malignant mesothelioma are found in patients exposed to asbestos. To elucidate the antitumor immune status caused by CD4(+) T cells exposed to asbestos, an in vitro T-cell model of long-term and low-level exposure to chrysotile asbestos was established from a human adult T-cell leukemia virus-1-immortalized human polyclonal T cell line, MT-2, and the resulting six sublines showed resistance to asbestos-induced apoptosis after more than 8 months of continuous exposure. The results of DNA microarray analysis showed that the expression of 139 genes was altered by long-term and low-level exposure to asbestos, and the profile was almost similar among the six sublines when compared with the original MT-2 cells that had never been exposed to asbestos. Pathway and network analysis indicated a down-regulation of IFN-gamma signaling and expression of CXC chemokine receptor 3 (CXCR3) in the sublines, whereas ELISA and flow cytometry analysis demonstrated a reduction in Th1-related IFN-gamma production and cell-surface CXCR3 expression. These findings suggest that chronic exposure to asbestos may reduce antitumor immune status in CD4(+) T cells, and that an in vitro T-cell model may be useful in identifying molecules related to the impairment of antitumor immune function.
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