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

Journal Article · Sat Mar 15 04:00:00 EDT 2014 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/J.TAAP.2014.01.018· OSTI ID:22423807

Zebedeo, Christian Nash; Davis, Chad ^[1]; Peña, Cecelia ^[2]; Ng, Kok Wei ^[1]

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1. Department of Biological Sciences, Idaho State University, Pocatello, ID (United States)
2. Northwest Nazarene University, Nampa, ID (United States)

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 μg/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{sub H}17 profile including IL-17, IL-6, TGF-β, and TNF-α. The frequency of ANA was increased in mice treated with erionite or amphibole compared to saline-treated mice. IL-17 and TNF-α 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. - Highlights: • Erionite, a fibrous mineral, is a current public health concern in the western USA. • Erionite exposure induces antinuclear autoantibodies in exposed mice. • Erionite induces a clear Th17 cytokine response in vitro and in vivo. • These responses were distinct from responses caused by asbestos. • These data in mice suggest that exposed humans may be at risk for autoimmunity.

• OSTI ID: 22423807
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 3 Vol. 275; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AMPHIBOLE
ANTIBODIES
ASBESTOS
BONE MARROW
COMPARATIVE EVALUATIONS
GROWTH FACTORS
HAZARDS
KIDNEYS
MACROPHAGES
MICE
NORTH DAKOTA
PHYSICAL PROPERTIES
PUBLIC HEALTH
TOXICITY