Skip Navigation

Publication Detail

Title: Specialized Pro-Resolving Lipid Mediators Regulate Ozone-Induced Pulmonary and Systemic Inflammation.

Authors: Kilburg-Basnyat, Brita; Reece, Sky W; Crouch, Miranda J; Luo, Bin; Boone, Andria D; Yaeger, Michael; Hodge, Myles; Psaltis, Christine; Hannan, Johanna L; Manke, Jonathan; Armstrong, Michael L; Reisdorph, Nichole; Tighe, Robert M; Shaikh, Saame Raza; Gowdy, Kymberly M

Published In Toxicol Sci, (2018 Jun 01)

Abstract: Exposure to ozone (O3) induces lung injury, pulmonary inflammation, and alters lipid metabolism. During tissue inflammation, specialized pro-resolving lipid mediators (SPMs) facilitate the resolution of inflammation. SPMs regulate the pulmonary immune response during infection and allergic asthma; however, the role of SPMs in O3-induced pulmonary injury and inflammation is unknown. We hypothesize that O3 exposure induces pulmonary inflammation by reducing SPMs. To evaluate this, male C57Bl/6J mice were exposed to filtered air (FA) or 1 ppm O3 for 3 h and necropsied 24 h after exposure. Pulmonary injury/inflammation was determined by bronchoalveolar lavage (BAL) differentials, protein, and lung tissue cytokine expression. SPMs were quantified by liquid chromatography tandem mass spectrometry and SPM receptors leukotriene B4 receptor 1 (BLT-1), formyl peptide receptor 2 (ALX/FPR2), chemokine-like receptor 1 (ChemR23), and SPM-generating enzyme (5-LOX and 12/15-LOX) expression were measured by real time PCR. 24 h post-O3 exposure, BAL PMNs and protein content were significantly increased compared to FA controls. O3-induced lung inflammation was associated with significant decreases in pulmonary SPM precursors (14-HDHA, 17-HDHA), the SPM PDX, and in pulmonary ALX/FPR2, ChemR23, and 12/15-LOX expression. Exogenous administration of 14-HDHA, 17-HDHA, and PDX 1 h prior to O3 exposure rescued pulmonary SPM precursors/SPMs, decreased proinflammatory cytokine and chemokine expression, and decreased BAL macrophages and PMNs. Taken together, these data indicate that O3-mediated SPM reductions may drive O3-induced pulmonary inflammation.

PubMed ID: 29471542 Exiting the NIEHS site

MeSH Terms: Animals; Bronchoalveolar Lavage Fluid/chemistry; Cytokines/genetics; Fatty Acids/analysis; Fatty Acids/metabolism; Gene Expression/drug effects; Leukotrienes/metabolism*; Lipid Metabolism/drug effects*; Lung/drug effects*; Lung/immunology; Lung/metabolism; Male; Mice, Inbred C57BL; Ozone/toxicity*; Pneumonia/chemically induced*; Pneumonia/metabolism; Pneumonia/pathology; Prostaglandins/metabolism*

Back
to Top