Erionite induces production of autoantibodies and IL-17 in C57BL/6 mice

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• 作者：Christian Nash Zebedeo^a ; Chad Davis^a ; Cecelia Peñ ; a^b ; Kok Wei Ng^a ; Jean C. Pfau^a ; ^{pfaujean@isu.edu" class="auth_mail}
• 关键词：ANA ; antinuclear autoantibodies ; BMDM ; bone marrow derived macrophages ; SLE ; systemic lupus erythematosus ; TGF ; transforming growth factor ; TNF ; tumor necrosis factor ; CBA ; cytometric bead array
• 刊名：Toxicology and Applied Pharmacology
• 出版年：15 March, 2014
• 年：2014
• 卷：275
• 期：3
• 页码：257-264
• 全文大小：917 K

文摘

Background

Erionite has similar chemical and physical properties to amphibole asbestos, which induces autoantibodies in mice. Current exposures are occurring in North Dakota due to the use of erionite-contaminated gravel. While erionite is known to cause mesothelioma and other diseases associated with asbestos, there is little known about its effects on the immune system.

Objectives

We performed this study to determine whether erionite evokes autoimmune reactions in mice.

Methods

Bone marrow derived macrophages (BMDM) were used to measure toxicity induced by erionite. Cytokine production by BMDM and splenocytes of C57BL/6 mice was examined by bead arrays and ELISA following exposure to erionite, amphiboles and chrysotile. Wild type C57BL/6 mice were exposed to saline, erionite, amphibole asbestos (Libby 6-Mix) or chrysotile through intratracheal instillations at equal mass (60 渭g/mouse). Seven months after exposure, sera were examined for anti-nuclear antibodies (ANA) and IL-17. Immunohistochemistry was used to detect immune complex deposition in the kidneys.

Results

Erionite and tremolite caused increased cytokine production belonging to the T_H17 profile including IL-17, IL-6, TGF-尾, and TNF-伪. The frequency of ANA was increased in mice treated with erionite or amphibole compared to saline-treated mice. IL-17 and TNF-伪 were elevated in the sera of mice treated with erionite. The frequency of immune complex deposition in the kidneys increased from 33% in saline-treated mice to 90% with erionite.

Conclusions

These data demonstrate that both erionite and amphibole asbestos induce autoimmune responses in mice, suggesting a potential for adverse effects in exposed communities.