Current Drug Targets

Francis J. Castellino
Kleiderer-Pezold Professor of Biochemistry
Director, W.M. Keck Center for Transgene Research
Dean Emeritus, College of Science
230 Raclin-Carmichael Hall, University of Notre Dame
Notre Dame, IN 46556
USA

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The Molecular Mechanisms of Glucocorticoids-Mediated Neutrophil Survival

Author(s): Arash S. Saffar, Heather Ashdown, Abdelilah S. Gounni.

Abstract:

Neutrophil-dominated inflammation plays an important role in many airway diseases including asthma, chronic obstructive pulmonary disease (COPD), bronchiolitis and cystic fibrosis. In cases of asthma where neutrophil-dominated inflammation is a major contributing factor to the disease, treatment with corticosteroids can be problematic as corticosteroids have been shown to promote neutrophil survival which, in turn, accentuates neutrophilic inflammation. In light of such cases, novel targeted medications must be developed that could control neutrophilic inflammation while still maintaining their antibacterial/anti-fungal properties, thus allowing individuals to maintain effective innate immune responses to invading pathogens. The aim of this review is to describe the molecular mechanisms of neutrophil apoptosis and how these pathways are modulated by glucocorticoids. These new findings are of potential clinical value and provide further insight into treatment of neutrophilic inflammation in lung disease.

Keywords: Apoptosis, glucocorticoid, inflammation, neutrophils, airway diseases, infection, caspases, Bcl-2, Dex, asthma, signaling pathway

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Article Details

VOLUME: 12
ISSUE: 4
Year: 2011
Page: [556 - 562]
Pages: 7
DOI: 10.2174/138945011794751555