Fueling the Mechanisms of Asthma: Increased Fatty Acid Oxidation in Inflammatory Immune Cells May Represent a Novel Therapeutic Target
| Autor: | Augusto C. Ochoa, Liqin Zheng, L. Del Valle, Maria Dulfary Sanchez-Pino, Amir A. Al-Khami, Jone Garay, Samuel C. Okpechi, A. H. Boulares, Salome V. Ibba, Paulo C. Rodriguez, Dorota Wyczechowska, Mohamed A. Ghonim, Kusma Pyakurel |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Chemokine Immunology Article 03 medical and health sciences Mice Immune system medicine Respiratory Hypersensitivity Immunology and Allergy Animals Molecular Targeted Therapy Beta oxidation Asthma House dust mite biology Fatty Acids Cancer Allergens Immunoglobulin E medicine.disease biology.organism_classification Pathophysiology Immunity Innate respiratory tract diseases Disease Models Animal 030104 developmental biology Immune System biology.protein Respiratory epithelium Cytokines Chemokines Oxidation-Reduction Biomarkers |
| Popis: | Background Increasing evidence has shown the close link between energy metabolism and the differentiation, function, and longevity of immune cells. Chronic inflammatory conditions such as parasitic infections and cancer trigger a metabolic reprogramming from the preferential use of glucose to the up-regulation of fatty acid oxidation (FAO) in myeloid cells, including macrophages and granulocytic and monocytic myeloid-derived suppressor cells. Asthma is another chronic inflammatory condition where macrophages, eosinophils, and polymorphonuclear cells play an important role in its pathophysiology. Objective We tested whether FAO might play a role in the development of asthma-like traits and whether the inhibition of this metabolic pathway could represent a novel therapeutic approach. Methods OVA and house dust mite (HDM)-induced murine asthma models were used in this study. Results Key FAO enzymes were significantly increased in the bronchial epithelium and inflammatory immune cells infiltrating the respiratory epithelium of mice exposed to OVA or HDM. Pharmacologic inhibition of FAO significantly decreased allergen-induced airway hyperresponsiveness, decreased the number of inflammatory cells, and reduced the production of cytokines and chemokines associated with asthma. Conclusions and clinical relevance These novel observations suggest that allergic airway inflammation increases FAO in inflammatory cells to support the production of cytokines, chemokines, and other factors important in the development of asthma. Inhibition of FAO may therefore provide a novel therapeutic approach for the treatment of asthma by re-purposing existing drugs that block FAO and are approved for the treatment of heart disease. This article is protected by copyright. All rights reserved. |
| Databáze: | OpenAIRE |
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