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Data from: Impact of soluble epoxide hydrolase inhibition on silica-induced pulmonary fibrosis, ectopic lymphoid neogenesis and autoantibody production in lupus-prone mice

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Jan 28, 2025 version files 201.48 KB

Abstract

Objective: Acute intranasal (IN) instillation of lupus-prone NZBWF1 mice with crystalline silica (cSiO2) triggers robust lung inflammation that drives autoimmunity. Prior studies in other preclinical models show that soluble epoxide hydrolase (sEH) inhibition promotes pro-resolving eicosanoid pathways that are protective against pulmonary inflammation. Herein, we assessed in NZBWF1 mice how acute IN cSiO2 exposure with or without the selective sEH inhibitor TPPU influences lipidomic, transcriptomic, proteomic, and histopathological biomarkers of inflammation, fibrosis and autoimmunity.

Methods: Female 6-wk-old NZBWF1 mice were fed control or TPPU-supplemented diets for 2 wk and then IN instilled with 2.5 mg cSiO2 or saline vehicle. Cohorts were terminated at 7d or 28d post-cSiO2 instillation (PI) and lungs analyzed for prostaglandins, cytokines/chemokines, gene expression, differential cell counts, histopathology, and autoantibodies.

Results: cSiO2-treatment induced prostaglandins, cytokines/chemokines, related gene expression, CD206+ monocytes, Ly6B.2+ neutrophils, CD3+ T cells, CD45R+ B cells, centriacinar inflammation, collagen deposition, ectopic lymphoid structure (ELS) neogenesis, and autoantibodies. While TPPU effectively inhibited sEH as reflected by skewed lipidomic profile in lung and decreased cSiO2 -induced monocytes, neutrophils, and lymphocytes in lung lavage fluid, it did not significantly impact other biomarkers.

Discussion: cSiO2 evoked robust pulmonary inflammation and fibrosis in NZBWF1 mice that was evident at 7d PI and that progressed to ELS development and autoimmunity by 28d PI. While sEH inhibition by TPPU of modestly suppressed cSiO2-induced cellularity changes and pulmonary fibrosis, it did not affect ELS formation or autoantibody responses elicited by the particle.