Rapid Induction of Pulmonary Inflammation, Autoimmune Gene Expression, and Ectopic Lymphoid Neogenesis Following Acute Silica Exposure in Lupus-Prone Mice.

Autor: Chauhan PS; Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, United States.; Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, United States., Wagner JG; Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, United States.; Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI, United States., Benninghoff AD; Department of Animal, Dairy and Veterinary Sciences, School of Veterinary Medicine, Utah State University, Logan, UT, United States., Lewandowski RP; Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI, United States., Favor OK; Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, United States.; Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, United States., Wierenga KA; Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, United States.; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, United States., Gilley KN; Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, United States., Ross EA; Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, United States., Harkema JR; Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, United States.; Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI, United States.; Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, United States., Pestka JJ; Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, United States.; Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, United States.; Department of Microbiology and Molecular Genetics, East Lansing, MI, United States.
Jazyk: angličtina
Zdroj: Frontiers in immunology [Front Immunol] 2021 Feb 23; Vol. 12, pp. 635138. Date of Electronic Publication: 2021 Feb 23 (Print Publication: 2021).
DOI: 10.3389/fimmu.2021.635138
Abstrakt: Occupational exposure to crystalline silica (cSiO 2 ) is etiologically associated with systemic lupus erythematosus (lupus) and other autoimmune diseases. cSiO 2 's autoimmune effects in humans can be mimicked chronically in female lupus-prone NZBWF1 mice following repeated exposure to the particle. However, the immediate and short-term effects of cSiO 2 in this widely used model of autoimmune disease are not well-understood. In the present study, we tested the hypothesis that a single acute cSiO 2 dose triggers early presentation of cellular, histopathological, transcriptomic, and protein biomarkers of inflammation and autoimmunity in lupus-prone mice. Eight-week old female NZBWF1 mice were intranasally instilled once with 2.5 mg cSiO 2 or saline vehicle and necropsied at 1, 7, 14, 21, and 28 d post-instillation (PI). Analyses of bronchoalveolar lavage fluid (BALF) and lung tissue revealed that by 7 d PI, acute cSiO 2 exposure persistently provoked: (i) robust recruitment of macrophages, neutrophils, and lymphocytes into the alveoli, (ii) cell death as reflected by increased protein, double-stranded DNA, and lactate dehydrogenase activity, (iii) elevated secretion of the cytokines IL-1α, IL-1β, IL-18, TNF-α, IL-6, MCP-1, and B cell activation factor (BAFF), and (iv) upregulation of genes associated with chemokines, proinflammatory cytokines, lymphocyte activation, and type I interferon signaling. The appearance of these endpoints was subsequently followed by the emergence in the lung of organized CD3 + T cells (14 d PI) and CD45R + B cells (21 d PI) that were indicative of ectopic lymphoid structure (ELS) development. Taken together, acute cSiO 2 exposure triggered a rapid onset of autoimmune disease pathogenesis that was heralded in the lung by unresolved inflammation and cell death, proinflammatory cytokine production, chemokine-driven recruitment of leukocytes, an interferon response signature, B and T cell activation, and ELS neogenesis. This short-term murine model provides valuable new insight into potential early mechanisms of cSiO 2 -induced lupus flaring and, furthermore, offers a rapid venue for evaluating interventions against respirable particle-triggered inflammation and autoimmunity.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Chauhan, Wagner, Benninghoff, Lewandowski, Favor, Wierenga, Gilley, Ross, Harkema and Pestka.)
Databáze: MEDLINE
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