Toxicology and applied pharmacology · 2014
Erionite induces production of autoantibodies and IL-17 in C57BL/6 mice.
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Zebedeo Christian Nash, Davis Chad, Peña Cecelia, Ng Kok Wei, Pfau Jean C
Аннотация
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 (60μg/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 TH17 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.
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 (60μg/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 TH17 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.
Предметные рубрики MeSH
AnimalsAntibodies, AntinuclearAntigen-Antibody ComplexAsbestos, AmphiboleAsbestos, SerpentineAutoimmunityBiomarkersCell SurvivalCells, CulturedDose-Response Relationship, DrugFemaleInhalation ExposureInterleukin-17KidneyMacrophagesMiceMice, Inbred C57BLSpleenTh1 CellsTh17 CellsTh2 CellsTime FactorsTumor Necrosis Factor-alphaUp-RegulationZeolites