DOI: 10.5061/dryad.wh70rxwx3
title: Data from: Impact of soluble epoxide hydrolase inhibition on silica-induced pulmonary fibrosis, ectopic lymphoid neogenesis and autoantibody production in lupus-prone mice

description: 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.
description: <strong>Profiling of proinflammatory cytokines and
 chemokines in the lung</strong> 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<sup>™</sup> 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.
description: # 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 Information Name: Ryan Lewandowski ORCID: None Institution: Michigan State University Address: 1129 Farm Ln, Office 218, East Lansing, MI 48824 Email: [lewando2@msu.edu](mailto:lewando2@msu.edu) Author/Alternate Contact Information Name: Dr. Lauren Heine ORCID: None Institution: Los Alamos National Laboratory Address: P.O. Box 1663, Los Alamos, NM 87545 Email: [lheine@lanl.gov](mailto:lheine@lanl.gov) Author/Alternate Contact Information Name: Vanessa Estrada ORCID: None Institution: Michigan State University Address: 567 Wilson Rd, Office 4183, East Lansing, MI 48824 Email: [estra100@msu.edu](mailto:estra100@msu.edu) Author/Alternate Contact Information Name: Dr. Elham Pourmand ORCID: None Institution: Michigan State University Address: 1355 Bogue St, Room B330, East Lansing, MI 48824 Email: [pourman1@.msu.edu](mailto:pourman1@msu.edu) Author/Alternate Contact Information Name: Megha Singhal ORCID: None Institution: Michigan State University Address: 1355 Bogue St, Room B330, East Lansing, MI 48824 Email: [singha28@msu.edu](mailto:singha28@msu.edu) Author/Alternate Contact Information Name: Dr. Jack Harkema ORCID: 0000-0003-4682-0824 Institution: Michigan State University Address: 1129 Farm Lane, Room 212, East Lansing, MI 48824 Email: [harkemaj@msu.edu](mailto:harkemaj@msu.edu) Author/Associate or Co-Investigator Information Name: Dr. Kin Sing Stephen Lee ORCID: 0000-0003-4541-3063 Institution: Michigan State University Address: Address: 1355 Bogue St, Room B330A, East Lansing, MI 48824 Email: [sing@msu.edu](mailto:sing@msu.edu) Date of data collection: 2022 Geographic location of data collection: 1) Michigan State University, East Lansing, MI 48824; 2) Eve Technologies Corporation, 3415A – 3 Ave., N. W., Calgary, AB Canada T2N 0M4. Information about funding sources that supported the collection of the data: National Institute of Environmental Health Sciences, RO1ES027353. ## Description of the data and file structure File List: File 1 - Mouse Cytokine and Chemokine 44-Plex Discovery Assay Array Data: contains weights of lung tissues homogenized (in mg) and results of the 44-plex assay (in pg/mL) Relationship between files, if important: N/A Additional related data collected that was not included in the current data package: Are there multiple versions of the dataset? No If yes, name of file(s) that was updated: Why was the file updated? When was the file updated? ### Methodological information #### **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. Describe any quality-assurance procedures performed on the data: People involved with sample collection, processing, analysis, and/or submission: Dr. Olivia McDonald, Dr. James Wagner, Ryan Lewandowski, Dr. Lauren Heine, Vanessa Estrada, Elham Pourmand, Megha Singhal, Dr. Jack Harkema, Dr. Kin Sing Stephen Lee, and Dr. James Pestka. ### Data-specific information for: Mouse Cytokine and Chemokine 44-Plex Discovery Assay Array Data Number of variables: Three variables - 1) silica exposure, 2) experimental diet (CON, TPPU), and 3) timepoint. Variable list: VEH - saline vehicle cSiO2 - crystalline silica, 2.5 mg CON - control AIN-93G diet TPPU - TPPU-amended diet (22.5 mg/kg diet) D7 - 7 days post-cSiO2 instillation D28 - 28 days post-cSiO2 instillation #### Sheet 1 - Key Description: Contains Sample ID numbers and corresponding experimental treatment groups with timepoints. Number of cases/rows: 49 Missing data codes: None Specialized formats of other abbreviations used: VEH_CON - VEH/CON experimental group cSiO2_CON - cSiO2/CON experimental group cSiO2_TPPU - cSiO2/TPPU experimental group D7 - 7 days post-cSiO2 instillation D28 - 28 days post-cSiO2 instillation #### Sheet 2 - Lung weights Description: Contains Sample ID numbers and corresponding lung tissue weights (in mg) that were homogenized for the Mouse Cytokine/Chemokine 44-Plex Discovery Assay® Array. Number of cases/rows: 49 Missing data codes: None Specialized formats of other abbreviations used: None #### Sheet 3 - 44-plex assay results Description: Original data report from Eve Technologies containing cytokine/chemokine concentrations from the Mouse Cytokine/Chemokine 44-Plex Discovery Assay Array (in pg/mL) and a detailed legend describing how to interpret the data. Number of cases/rows: 102 Missing data codes: None Specialized formats of other abbreviations used: FI - Fluorescent Intensity Obs. Conc. - Observed Concentration Exp. Conc. - Expected Concentration OOR - Out of Range OOR &gt; - Out of Range Above the Standard Curve OOR &lt; - Out of Range Below the Standard Curve Orange Data - Extrapolated Value Blank Cell or --- - Value Not Available Blue Highlighted Cell - Low Bead Count Or No Beads Blue Data - Partially Filtered Green Highlighted Cell - Possible Sample Saturation Red Highlighted Cell - Low Sample Volume ## Sharing/Access information Licenses/restrictions placed on the data: None Links to publications that cite or use the data: [https://doi.org/10.1080/08958378.2024.2413373](https://doi.org/10.1080/08958378.2024.2413373) Links to other publicly accessible locations of the data: None Links/relationships to ancillary data sets: None Was data derived from another source? No Recommended citation for this dataset: Not at this time