Sputum inflammatory cells from patients with allergic rhinitis and asthma have decreased inflammasome gene expression

Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC.
The Journal of allergy and clinical immunology (Impact Factor: 11.48). 08/2011; 128(4):900-3. DOI: 10.1016/j.jaci.2011.08.012
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Available from: June W Brickey, Apr 25, 2014
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    The Journal of allergy and clinical immunology 01/2012; 129(1):259-61.e1-2. DOI:10.1016/j.jaci.2011.11.007 · 11.48 Impact Factor
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    ABSTRACT: Atopic asthmatic patients are reported to be more sensitive to the effects of environmental endotoxin (LPS) than healthy volunteers (HVs). It is unknown whether this sensitivity is due to dysregulated inflammatory responses after LPS exposure in atopic asthmatic patients. We sought to test the hypothesis that atopic asthmatic patients respond differentially to inhaled LPS challenge compared with HVs. Thirteen allergic asthmatic (AA) patients and 18 nonallergic nonasthmatic subjects (healthy volunteers [HVs]) underwent an inhalation challenge to 20,000 endotoxin units of Clinical Center Reference Endotoxin (LPS). Induced sputum and peripheral blood were obtained at baseline and 6 hours after inhaled LPS challenge. Sputum and blood samples were assayed for changes in inflammatory cell numbers and cytokine and cell-surface marker levels on monocytes and macrophages. The percentage of neutrophils in sputum (%PMN) in induced sputum similarly and significantly increased in both HVs and AA patients after inhaled LPS challenge. However, the absolute numbers of leukocytes and PMNs recruited to the airways were significantly lower in AA patients compared with those seen in HVs with inhaled LPS challenge. Sputum levels of IL-6 and TNF-α were significantly increased in both cohorts, but levels of IL-1β and IL-18 were only significantly increased in the HV group. Cell-surface expression of Toll-like receptors 4 and 2 were significantly enhanced only in the HV group. The airway inflammatory response to inhaled LPS challenge is blunted in AA patients compared with that seen in HVs and accompanied by reductions in airway neutrophilia and inflammasome-dependent cytokine production. These factors might contribute to increased susceptibility to airway microbial infection or colonization in AA patients.
    The Journal of allergy and clinical immunology 07/2012; 130(4):869-876.e2. DOI:10.1016/j.jaci.2012.05.026 · 11.48 Impact Factor
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    ABSTRACT: Asthma is characterized by airway inflammation, airway hyperresponsiveness and airway remodelling. Uncontrolled airway inflammation or repeated asthma exacerbations can lead to airway remodelling which cannot be reversed by current pharmacological treatment, and consequently leads to decline in lung function. Thus, it is critical to understand airway inflammation in asthma and infectious exacerbation. The inflammasome has emerged as playing a key role in innate immunity and inflammation. Upon ligand sensing, inflammasome components assemble and self-oligomerize, leading to caspase-1 activation and maturation of pro-IL-1β and pro-IL-18 into bioactive cytokines. These bioactive cytokines then play a pivotal role in the initiation and amplification of inflammatory processes. In addition to facilitating the proteolytic activation of IL-1β and IL-18, inflammasomes also participate in cell death through caspase-1-mediated pyroptosis. In this review we describe the structure and function of the inflammasome and provide an overview of our current understanding of role of the inflammasome in airway inflammation. We focus on nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome as it is the best characterized subtype shown expressed in airway and considered to play a key role in chronic airway diseases such as asthma. This article is protected by copyright. All rights reserved.
    Clinical & Experimental Allergy 10/2013; 44(2). DOI:10.1111/cea.12206 · 4.77 Impact Factor
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