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

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 upregulates pro-resolving lipid metabolites 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-week-old NZBWF1 mice were fed control or TPPU-supplemented diets for 2 weeks then IN instilled with 2.5 mg cSiO₂ or saline vehicle. Cohorts w

SUBMITTER: McDonald OF 

PROVIDER: S-EPMC11606782 | biostudies-literature | 2024 Aug-Sep

REPOSITORIES: biostudies-literature