Butyrate ameliorates allergic airway inflammation by limiting eosinophil trafficking and survival

Lung eosinophilia is a hallmark of asthma, and eosinophils are believed to play a crucial role in the pathogenesis of allergic inflammatory diseases. Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, are produced in high amounts in the gastrointestinal tract by commensal ba...

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Bibliographic Details
Published in:Journal of allergy and clinical immunology 2019-09, Vol.144 (3), p.764-776
Main Authors: Theiler, Anna, Bärnthaler, Thomas, Platzer, Wolfgang, Richtig, Georg, Peinhaupt, Miriam, Rittchen, Sonja, Kargl, Julia, Ulven, Trond, Marsh, Leigh M., Marsche, Gunther, Schuligoi, Rufina, Sturm, Eva M., Heinemann, Akos
Format: Article
Language:English
Subjects:
Acetic acid
Acetylation
Adhesion
Allergens
allergic airway inflammation
Allergies
Animal models
Animals
Anti-Inflammatory Agents - pharmacology
Anti-Inflammatory Agents - therapeutic use
Apoptosis
Apoptosis - drug effects
Asthma
Asthma - drug therapy
Asthma - genetics
Asthma - immunology
butyrate
Butyrates - pharmacology
Butyrates - therapeutic use
Calcium (mitochondrial)
Calcium ions
Cell Movement - drug effects
Chemical compounds
Cytokines
Endothelium
Eosinophilia
Eosinophils
Eosinophils - drug effects
Eosinophils - immunology
Eosinophils - physiology
Fatty acids
Female
Flow cytometry
Gastrointestinal tract
Gene Expression Regulation - drug effects
Histone deacetylase
Histones
Humans
Inflammation
Inflammatory diseases
Leukocyte migration
Leukocytes (eosinophilic)
Lungs
Membrane potential
Mice, Inbred BALB C
Mitochondria
Neutrophils
Ovalbumin
Pathogenesis
Propionic acid
Proteins
Pulmonary Eosinophilia - drug therapy
Pulmonary Eosinophilia - genetics
Pulmonary Eosinophilia - immunology
Respiratory tract
Respiratory tract diseases
Short-chain fatty acid
Software
Surface markers
Survival
Trichostatin A
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Summary:Lung eosinophilia is a hallmark of asthma, and eosinophils are believed to play a crucial role in the pathogenesis of allergic inflammatory diseases. Short-chain fatty acids (SCFAs), such as acetate, propionate, and butyrate, are produced in high amounts in the gastrointestinal tract by commensal bacteria and can be absorbed into the bloodstream. Although there is recent evidence that SCFAs are beneficial in allergic asthma models, the effect on eosinophils has remained elusive. The role of SCFAs was investigated in human eosinophil function and a mouse model of allergic asthma. Eosinophils were purified from self-reported allergic or healthy donors. Migration, adhesion to the endothelium, and eosinophil survival were studied in vitro. Ca2+ flux, apoptosis, mitochondrial membrane potential, and expression of surface markers were determined by using flow cytometry and in part by using real-time PCR. Allergic airway inflammation was assessed in vivo in an ovalbumin-induced asthma model by using invasive spirometry. For the first time, we observed that SCFAs were able to attenuate human eosinophils at several functional levels, including (1) adhesion to the endothelium, (2) migration, and (3) survival. These effects were independent from GPR41 and GPR43 but were accompanied by histone acetylation and mimicked by trichostatin A, a pan–histone deacetylase inhibitor. In vivo butyrate ameliorated allergen-induced airway and lung eosinophilia, reduced type 2 cytokine levels in bronchial fluid, and improved airway hyperresponsiveness in mice. These in vitro and in vivo findings highlight the importance of SCFAs, especially butyrate as a promising therapeutic agent in allergic inflammatory diseases. [Display omitted]
ISSN:0091-6749
1097-6825
DOI:10.1016/j.jaci.2019.05.002