Asthma is a disorder that causes the airways of the lungs to swell and constrict, making sufferers wheeze, cough and grapple with shortness of breath and chest tightness. The Journal of Biological Chemistry has played, and will continue to play, a critical role in better understanding the molecular basis for the illness and, ultimately, identifying improved therapies for patients. To highlight JBC authors’ contributions to the study of the molecular basis of asthma, the late JBC associate editor Dale J. Benos first conceived a thematic minireview series on asthma; the series was later completed by associate editor Luke O’Neill.
Asthma research is multidisciplinary and includes immunology, gene expression, signal transduction and ion channel regulation. In the first minireview, Miguel A. Valverde, Gerard Cantero-Recasens, Anna Garcia-Elias, Carole Jung, Amado Carreras-Sureda and Ruben Vicente at the Pomeu Fabra University in Spain discuss ion channels. In the airways, ion channels are involved in the production of epithelial-based hydroelectrolytic secretions and in the control of intracellular Ca2+ levels that activate almost all lung cells. Ion channels are the focus of many studies that seek to better understand asthma pathophysiological mechanisms or to identify therapeutic targets. The review covers animal models, molecular and genetic studies, and clinical observations that relate ion channel activity to the pathogenesis of asthma.
Allergic asthma is a chronic, airway inflammatory disease in which patients exposed to allergens suffer from intermittent attacks of breathlessness, airway hyper-reactivity, wheezing and coughing. Allergic asthma stems from a complex interplay between genetic and environmental factors. The second minireview, by Anil B. Mukherjee and Zhongjian Zhang at the U.S. National Institutes of Health, discusses how genetic and environmental factors culminate in allergic asthma. The authors describe how difficult it is to study allergic responses in asthma because the complex array of signaling reactions is not easily reproduced in animal models.
The third minireview also takes on certain aspects of allergic asthma. In particular, it focuses on elevated IgE levels and increased IgE sensitization as disease hallmarks. Genentech’s Lawren C. Wu notes that IgE binding to high-affinity FcεRI and the low-affinity FcεRII/CD23 receptors should be an important goal of future research. Additional points for investigation include “novel cell surface and intracellular mediators of FcεRI activation, mechanisms of intracellular calcium signaling, and new inhibitory proteins that negatively regulate parts of the signaling network downstream of FcεRI activation.”
Peter J. Barnes at Imperial College London covers signaling pathways of existing – and quite effective – therapies for asthma in the fourth minireview. Bronchodilators, like the β2-adrenergic receptor (β2AR) agonists, relax airway smooth muscle cells by increasing cyclic AMP concentrations and opening large conductance Ca2+ channels. Glucocorticoids are anti-inflammatory treatments that turn off multiple activated inflammatory genes. Beneficial molecular interactions between β2AR and glucocorticoid-activated pathways exist. Barnes says that our relatively good understanding of how current asthma therapies work in terms of their biochemical mechanisms will help to tweak existing treatments and invent new ones.
This thematic minireview series, like its predecessors, aims to link biochemical processes to an important clinical challenge. Over the past 50 years, both the incidence and the severity of asthma have increased globally, further burdening national public-health services. Still forthcoming in this thematic series are two minireviews, one on exercise-induced asthma by Lisa M. Schwiebert at the University of Alabama and the other on myeloid-derived regulatory cells and redox control in asthma by David D. Chaplin at the University of Alabama.
Visit this thematic series online at http://www.jbc.org/site/thematics/asthma.
Rajendrani Mukhopadhyay (firstname.lastname@example.org) is a senior science writer and editor for ASBMB.