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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Kilburg-Basnyat, B; Reece, SW; Crouch, MJ; Luo, B; Boone, AD; Yaeger, M; Hodge, M; Psaltis, C; Hannan, JL; Manke, J; Armstrong, ML; Reisdorph, N; Tighe, RM; Shaikh, SR; Gowdy, KM

Published Date

  • June 1, 2018

Published In

Volume / Issue

  • 163 / 2

Start / End Page

  • 466 - 477

PubMed ID

  • 29471542

Pubmed Central ID

  • 29471542

Electronic International Standard Serial Number (EISSN)

  • 1096-0929

Digital Object Identifier (DOI)

  • 10.1093/toxsci/kfy040

Language

  • eng

Conference Location

  • United States