Do mast cells link obesity and asthma?

Authors

  • N. Sismanopoulos,

    1. Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine, Boston, MA, USA
    Current affiliation:
    1. Department of Internal Medicine, St. Elizabeth's Medical Center, Boston, MA, USA
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  • D.-A. Delivanis,

    1. Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine, Boston, MA, USA
    Current affiliation:
    1. Department of Internal Medicine, University of Connecticut Medical Center, Farmington, CT, USA
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  • D. Mavrommati,

    1. Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine, Boston, MA, USA
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  • E. Hatziagelaki,

    1. Second Department of Internal Medicine, Athens University Medical School, ‘Attikon’ General Hospital, Athens, Greece
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  • P. Conti,

    1. Department of Oncology and Experimental Medicine, University of Chieti-Pescara, Chieti, Italy
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  • T. C. Theoharides

    Corresponding author
    1. Department of Biochemistry, Tufts University School of Medicine, Boston, MA, USA
    2. Department of Internal Medicine, Tufts University School of Medicine and Tufts Medical Center, Boston, MA, USA
    • Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine, Boston, MA, USA
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  • Edited by: Marek Sanak

Correspondence

Theoharis C. Theoharides, Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine, 136 Harrison Avenue Suite J304, Boston, MA 02111, USA.

Tel.: +1 617 636 6866

Fax: +1 617 636 2456

E-mail: theoharis.theoharides@tufts.edu

Abstract

Asthma is a chronic inflammatory disease of the lungs. Both the number of cases and severity of asthma have been increasing without a clear explanation. Recent evidence suggests that obesity, which has also been increasing alarmingly, may worsen or precipitate asthma, but there is little evidence of how obesity may contribute to lung inflammation. We propose that mast cells are involved in both asthma and obesity by being the target and source of adipocytokines, ‘alarmins’ such as interleukin-9 (IL-9) and interleukin-33 (IL-33), and stress molecules including corticotropin-releasing hormone (CRH) and neurotensin (NT), secreted in response to the metabolic burden. In particular, CRH and NT have synergistic effects on mast cell secretion of vascular endothelial growth factor (VEGF). IL-33 augments VEGF release induced by substance P (SP) and tumor necrosis factor (TNF) release induced by NT. Both IL-9 and IL-33 also promote lung mast cell infiltration and augment allergic inflammation. These molecules are also expressed in human mast cells leading to autocrine effects. Obese patients are also less sensitive to glucocorticoids and bronchodilators. Development of effective mast cell inhibitors may be a novel approach for the management of both asthma and obesity. Certain flavonoid combinations may be a promising new treatment approach.

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