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J Proteome Res. 2014 Aug 01;13(8):3771-3782. doi: 10.1021/pr5003615. Epub 2014 Jul 02.

Metabolomics Reveals Inflammatory-Linked Pulmonary Metabolic Alterations in a Murine Model of House Dust Mite-Induced Allergic Asthma.

Journal of proteome research

Wanxing Eugene Ho, Yong-Jiang Xu, Chang Cheng, Hong Yong Peh, Steven R Tannenbaum, W S Fred Wong, Choon Nam Ong

Affiliations

  1. Singapore-MIT Alliance for Research and Technology (SMART), Singapore 138602.
  2. Key Laboratory of Insect Development and Evolutionary Biology, Chinese Academy of Sciences , Shanghai 200032, China.
  3. Department of Gastroenterology & Hepatology, Singapore General Hospital , Singapore 169608.
  4. Department of Biological Engineering and Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.

PMID: 24956233 DOI: 10.1021/pr5003615

Abstract

Although the house dust mite (HDM) is a major environmental aeroallergen that promotes the pathogenesis and severity of allergic asthma, it remains elusive if HDM exposures can induce global metabolism aberrations during allergic airway inflammation. Using an integrated gas and liquid chromatography mass spectrometry-based metabolomics and multiplex cytokine profile analysis, metabolic alterations and cytokine changes were investigated in the bronchoalveolar lavage fluid (BALF), serum, and lung tissues in experimental HDM-induced allergic asthma. Allergic pulmonary HDM exposures lead to pronounced eosinophilia, neutrophilia, and increases in inflammatory cytokines. Metabolomics analysis of the BALF, serum, and lung tissues revealed distinctive compartmental metabolic signatures, which included depleted carbohydrates, increased energy metabolites, and consistent losses of sterols and phosphatidylcholines. Pearson correlation analysis uncovered strong associations between specific metabolic alterations and inflammatory cells and cytokines, linking altered pulmonary metabolism to allergic airway inflammation. The clinically prescribed glucocorticoid prednisolone could modulate airway inflammation but was ineffective against the reversal of many HDM-induced metabolic alterations. Collectively, metabolomics reveal comprehensive pulmonary metabolic signatures in HDM-induced allergic asthma, with specific alterations in carbohydrates, lipids, sterols, and energy metabolic pathways. Altered pulmonary metabolism may be a major underlying molecular feature involved during HDM-induced allergic airway inflammation, linked to inflammatory cells and cytokines changes.

Keywords: allergy; corticosteroids; gas chromatography; inflammation; liquid chromatography; mass spectrometry; metabolome

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