Soluble epoxide hydrolase inhibitor attenuates inflammation and airway hyperresponsiveness in mice

Jun Yang, Jennifer Bratt, Lisa Franzi, Jun Yan Liu, Guodong Zhang, Amir Zeki, Christoph F A Vogel, Keisha Williams, Hua Dong, Yanping Lin, Sung Hee Hwang, Nicholas Kenyon, Bruce D. Hammock

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Control of airway inflammation is critical in asthma treatment. Soluble epoxide hydrolase (sEH) has recently been demonstrated as a novel therapeutic target for treating inflammation, including lung inflammation. We hypothesized that pharmacological inhibition of sEH can modulate the inflammatory response in a murine ovalbumin (OVA) model of asthma. BALB/c mice were sensitized and exposed to OVA over 6 weeks. A sEH inhibitor (sEHI) was administered for 2 weeks. Respiratory system compliance, resistance, and forced exhaled nitric oxide were measured. Lung lavage cell counts were performed, and selected cytokines and chemokines in the lung lavage fluid were measured. A LC/MS/MS method was used to measure 87 regulatory lipids mediators in plasma, lung tissue homogenates, and lung lavage fluid. The pharmacological inhibition of sEH increased concentrations of the antiinflammatory epoxy eicosatrienoic acids and simultaneously decreased the concentrations of the proin flammatory dihydroxyeicosatrienoic acids and dihydroxyoctadecenoic acids. All monitored inflammatory markers, including FeNO levels, and total cell and eosinophil numbers in the lung lavage of OVA-exposedmice were reduced by sEHI. The type 2 T helper cell (Th2) cytokines (IL-4, IL-5) and chemokines (Eotaxin and RANTES) were dramatically reduced after sEHI administration. Resistance and dynamic lung compliance were also improved by sEHI. We demonstrated that sEHI administration attenuates allergic airway inflammation and airway responsiveness in a murine model. sEHI may have potential as a novel therapeutic strategy for allergic asthma.

Original languageEnglish (US)
Pages (from-to)46-55
Number of pages10
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume52
Issue number1
DOIs
StatePublished - Jan 1 2015

Keywords

  • Asthma
  • Inflammation
  • Lipid mediators
  • Soluble epoxide hydrolase
  • Type 2 T helper cell cytokines

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

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    Yang, J., Bratt, J., Franzi, L., Liu, J. Y., Zhang, G., Zeki, A., Vogel, C. F. A., Williams, K., Dong, H., Lin, Y., Hwang, S. H., Kenyon, N., & Hammock, B. D. (2015). Soluble epoxide hydrolase inhibitor attenuates inflammation and airway hyperresponsiveness in mice. American Journal of Respiratory Cell and Molecular Biology, 52(1), 46-55. https://doi.org/10.1165/rcmb.2013-0440OC