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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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, cyto..., Profiling of proinflammatory cytokines and chemokines in the lung Lung tissues were weighed and homogenized in RIPA Lysis and Extraction Buffer (Thermo Fisher Scientific) using TissueLyser II (Qiagen, Germantown, MD) to yield 20% (w/v) homogenate in buffer. Total protein in each sample was quantified using a Pierce⢠BCA Protein Assay Kit (Thermo Fisher Scientific) and sample absorbances measured using a FilterMax F3 Multimode plate reader (Molecular Devices, San Jose, CA) set to 562 nm. Samples were normalized to a total protein concentration of 1000 µg/ml by adding the appropriate volume of RIPA buffer. Then, 100-µl sample aliquots were shipped to Eve Technologies (Calgary, Alberta, Canada) for quantification of homogenate cytokines and chemokines using Mouse Cytokine/Chemokine 44-Plex Discovery Assay® Array. Resultant cytokine and chemokine levels were normalized to the original weight of lung tissue homogenized per animal and reported in units of pg/g lung tissue., , # Data from: Impact of Soluble Epoxide Hydrolase Inhibition on Silica-Induced Pulmonary Fibrosis, Ectopic Lymphoid Neogenesis, and Autoantibody Production in Lupus-Prone Mice [https://doi.org/10.5061/dryad.wh70rxwx3](https://doi.org/10.5061/dryad.wh70rxwx3) Author/Principal Investigator Information Name: Dr. Olivia McDonald ORCID: 0000-0001-9164-7077 Institution: Michigan State University Address: 567 Wilson Rd, Office 4183, East Lansing, MI 48824 Email: [favoroli@msu.edu](mailto:favoroli@msu.edu) Author/Associate or Co-Investigator Information Name: Dr. James Pestka ORCID: 0000-0003-4689-2756 Institution: Michigan State University Address: 567 Wilson Rd, Office 4176, East Lansing, MI 48824 Email: [pestka@msu.edu](mailto:pestka@msu.edu) Author/Alternate Contact Information Name: Dr. James Wagner ORCID: None Institution: Michigan State University Address: 1129 Farm Ln, Room 211, East Lansing MI 48824 Email: [wagnerja@msu.edu](mailto:wagnerja@msu.edu) Author/Alternate Contact Informa...
