Data from: Impact of soluble epoxide hydrolase inhibition on silica-induced pulmonary fibrosis, ectopic lymphoid neogenesis and autoantibody production in lupus-prone mice
Data files
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.
README: 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
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
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
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
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
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
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
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
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
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
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
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 > - Out of Range Above the Standard Curve
OOR < - 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
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
Methods
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.