A Targeted Lipidomic Reveals CYP450-Derived Oxylipin Linked to the Inflammatory Response by Polycyclic Aromatic Hydrocarbon Exposure in Children

Yifeng Dai, Zhiheng Cheng, Zhijun Zeng, Machteld N. Hylkema, Marijke M. Faas, Xia Huo*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Polycyclic aromatic hydrocarbon (PAH) exposure is a cause of chronic inflammation. The effect of PAHs on bioactive lipid mediators involved in the inflammatory process remains largely unknown. This study measured ten urinary monohydroxy-PAHs (OH-PAHs), 54 plasma oxylipins, and inflammation-related markers. Children with high PAH exposure had higher levels of ten OH-PAHs, (±)18-HETE, 19(S)-HETE, 5,6-DiHETrE, 9,10-DiHOME, more monocytes, interleukin (IL)-10, tumor necrosis factor (TNF)-α and IL-6 than those with low PAH exposure (all p < 0.05). The ƩOH-PAHs were inversely correlated to the levels of anti-inflammatory oxylipins, including 5,6-EET (p for trend = 0.007), 11,12-EET (p for trend = 0.035), 14,15-EET (p for trend = 0.022), and 16(17)-EpDPE (p for trend = 0.043), but positively associated with pro-inflammatory 9,10-DiHOME (p for trend < 0.001). Mediation analyses indicated that cytochrome P450 (CYP)-derived 9,10-DiHOME mediated a separate 42.7%, 31.1%, 57.8%, and 38.5% of the associations between OH-PAHs and monocytes, IL-6, IL-10, TNF-α (p = 0.017, 0.014, 0.005 and 0.012, respectively). Our study suggests that CYP-derived oxylipins can be considered sensitive lipid mediators to signal the early inflammation response to PAH exposure.

Original languageEnglish
Pages (from-to)455-466
Number of pages12
JournalExposure and Health
Volume15
Issue number2
DOIs
Publication statusPublished - Jun 2023
Externally publishedYes

Keywords

  • Cytokine
  • Inflammation
  • Metabolomic
  • Monocyte
  • PAHs
  • PUFAs

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