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

Our plain-English summary of Erionite induces production of autoantibodies and IL-17 in C57BL/6 mice, by C.N. Zebedeo, C. Davis, C. Peña, et al (Toxicology and Applied Pharmacology, 2014).

The study

• Authors: C.N. Zebedeo, C. Davis, C. Peña, K.W. Ng, J.C. Pfau
• Journal: Toxicology and Applied Pharmacology
• Published: 2014;275(3):257-64
• Cited by: 29 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

Copyright © 2014 Elsevier Inc. All rights reserved.

In plain English

This laboratory study tested whether erionite, a fibrous zeolite, provokes autoimmune responses in mice like those linked to amphibole asbestos. Bone marrow derived macrophages were exposed in culture to erionite, chrysotile, tremolite, Libby 6-Mix or wollastonite, and mixed splenocytes to erionite, tremolite or chrysotile; separately, wild type female C57BL/6 mice received two intratracheal instillations of 30 μg of erionite, Libby 6-Mix or chrysotile (60 μg per mouse) or saline vehicle, with sera tested seven months later and kidneys examined in the erionite and saline groups only. In splenocyte cultures at 35 μg/cm2, erionite and tremolite significantly increased IL-6, IL-17 and TNF-alpha, while chrysotile decreased them. Antinuclear antibodies were found in 8 of 10 erionite-treated mice (80%, p = 0.005) and 8 of 11 Libby 6-Mix mice (73%, p = 0.018) versus 4 of 18 saline mice (22%); chrysotile (3 of 7, 42%) did not differ significantly. Kidney IgG deposition occurred in 9 of 10 erionite mice versus 3 of 9 saline mice. The authors concluded that erionite and amphibole asbestos induce autoimmune responses in mice.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Experimental animal and in vitro cell culture study
• Who was studied: Female wild type C57BL/6 mice (ANA groups: saline n=18, erionite n=10, Libby 6-Mix n=11, chrysotile n=7; kidney staining: saline n=9, erionite n=10), plus bone marrow derived macrophages and mixed splenocytes from C57BL/6 mice; Idaho State University
• Exposure: Oregon erionite, Korean tremolite, Libby 6-Mix amphibole (tremolite, other amphiboles, winchite and richterite), chrysotile and wollastonite; cultures at 0 to 105 μg/cm2 with most experiments at 35 μg/cm2; mice given two intratracheal instillations of 30 μg one week apart, with saline as the control
• Main results:
  • In splenocyte cultures exposed to erionite, tremolite or chrysotile, the TH17 cytokines IL-6, IL-17 and TNF-alpha were significantly increased by erionite and tremolite (at least two-fold) and decreased by chrysotile
  • In splenocyte cultures, erionite increased IFN-gamma nearly 4-fold and TNF-alpha nearly 9-fold but decreased IL-2 by about half; tremolite increased TNF-alpha about 4-fold and decreased IFN-gamma; chrysotile decreased all three TH1 cytokines
  • IL-10 (TH2) rose about 9-fold in erionite-exposed splenocytes; IL-4 showed no meaningful change
  • TGF-beta production by bone marrow derived macrophages increased after erionite and tremolite exposure
  • Wollastonite also significantly increased TGF-beta above control, but to a significantly lower level than erionite
  • BMDM viability fell below 90% for all fibers above 35 μg/cm2; for erionite the change reached statistical significance (p less than 0.05) at 50 μg/cm2
  • BMDM TNF-α production was raised above control by erionite and all asbestos fibers, erionite greater than amphibole greater than chrysotile; wollastonite did not induce it
  • Serum antinuclear antibodies seven months after instillation: saline 4/18 (22%), erionite 8/10 (80%), chrysotile 3/7 (42%), Libby 6-Mix 8/11 (73%); only erionite (p = 0.005) and Libby 6-Mix (p = 0.018) differed significantly from saline
  • Kidney immune complex staining, done only in the erionite and saline groups: IgG deposition in 9 of 10 erionite-exposed mice versus 3 of 9 saline-exposed mice
  • Serum TNF-α and IL-17 were elevated in erionite-exposed mice compared with saline (erionite n=5, saline n=4)
  • Antibody isotypes: erionite and tremolite increased IgG1 and IgG2a and raised IgM at least two-fold; chrysotile produced no change
• The authors' conclusion: The authors concluded that both erionite and amphibole asbestos induce autoimmune responses in mice, suggesting potential adverse effects in exposed communities, and that erionite may behave similarly to amphibole asbestos in promoting autoantibody production
• Limitations the authors state:
  • The authors stated that interpretation of the TH1 cytokine results will be more meaningful only once responses to erionite are examined in other mouse strains and in humans, cytokine levels not having been measured in erionite-exposed people
  • The authors stated that the proposed apoptosis mechanism for erionite requires further study
  • The authors stated that the significance of the IL-10 increase requires further study in humans
  • The authors stated that further studies screening for autoantibodies in erionite-exposed human populations are needed to establish a relationship in humans

Topics

The National Library of Medicine indexes this study under subjects our site covers: Chrysotile.

Medical terms in this study, explained in our Lexicon: erionite, Amphibole Asbestos, Mesothelioma, Macrophage, Cytokine, Amphibole Group, Chrysotile, Immunohistochemistry.

Related studies

• Amphibole, but not chrysotile, asbestos induces anti-nuclear autoantibodies and IL-17 in C57BL/6 mice — A. Ferro, C.N. Zebedeo, et al. (2014)
• Asbestos-induced autoimmunity in C57BL/6 mice — J.C. Pfau, J.J. Sentissi, et al. (2008)
• Autoantibodies from mice exposed to Libby amphibole asbestos bind SSA/Ro52-enriched apoptotic blebs of murine macrophages — D.J. Blake, S.A. Wetzel, et al. (2008)
• Asbestos and erionite fibres can induce mutations in human lymphocytes that result in loss of heterozygosity — K. Both, D.W. Henderson, et al. (1994)
• Characterization of pulmonary responses in mice to asbestos/asbestiform fibers using gene expression profiles — N. Yanamala, E.R. Kisin, et al. (2018)
• Libby amphibole-induced mesothelial cell autoantibodies promote collagen deposition in mice — J. Gilmer, K. Serve, et al. (2016)

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