Airway smooth muscle and immunomodulation in acute exacerbations of airway disease

Airways Biology Initiative, Pulmonary, Allergy and Critical Care Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104-3413, USA.
Immunological Reviews (Impact Factor: 10.12). 07/2011; 242(1):178-85. DOI: 10.1111/j.1600-065X.2011.01022.x
Source: PubMed


Airway smooth muscle (ASM) manifests a hyperresponsive phenotype in airway disorders such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis. Current evidence also suggests that ASM modulates immune responses by secreting mediators and expressing cell surface molecules. Such processes amplify or dampen inflammation by inflammatory cells in the airways or by altering cellular responses to viruses, bacteria, or pathogens known to exacerbate airways diseases.

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Available from: Cynthia Koziol-White, Mar 20, 2014
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    • "There are two primary levels of control regarding Ca 2þ signalling: the regulation of [Ca 2þ ] i and the sensitivity of " effector " proteins to changes in [Ca 2þ ] i . Understanding the molecular mechanisms underlying these pathways is essential to gain insights into various respiratory diseases including asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) [2], and is the focus of the current review. "
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    ABSTRACT: Free calcium ions within the cytosol serve as a key secondary messenger system for a diverse range of cellular processes. Dysregulation of cytosolic Ca2+ handling in airway smooth muscle (ASM) has been implicated in asthma, and it has been hypothesised that this leads, at least in part, to associated changes in both the architecture and function of the lung. Significant research is therefore directed towards furthering our understanding of the mechanisms which control ASM cytosolic calcium, in addition to those regulating the sensitivity of its downstream effector targets to calcium. Key aspects of the recent developments in this field were discussed at the 8th Young Investigators' Symposium on Smooth Muscle (2013, Groningen, The Netherlands), and are outlined in this review.
    Pulmonary Pharmacology &amp Therapeutics 12/2014; 29(2). DOI:10.1016/j.pupt.2014.05.001 · 2.94 Impact Factor
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    • "Steroid treatment has been shown to decrease this muscle mass in animal but not human studies [13] and this was confirmed in our study, too. TNF-α is shown to induce airway hyperresponsiveness via activation of NF-κB and upregulation of CD38 [21] [22] [23]. Thus, TNF-α blockage would be expected to decrease smooth muscle mass and hyperreactivity. "
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    ABSTRACT: Antagonism of TNF-α may interfere with remodeling in asthmatic airway. The aim of the study was to compare the influence of TNF antagonism and corticosteroid treatment on epithelial, smooth muscle and basement membrane component of airway remodeling in an experimental murine model of chronic asthma. We used 30 BALB/c mice. Group 1 not exposed to ovalbumin or any medication was designated as control group. Chronic asthma model was achieved in the other three groups with intraperitoneal (IP) and inhaled ovalbumin. Then, Group 2 received IP saline, Group 3 received IP dexamethasone and Group 4 received IP etanercept. Histomorphological examination for epithelial, subepithelial smooth muscle and basement membrane thickness as well as goblet cells and mast cells was performed on samples isolated from middle zone of left lung. Etanercept treatment led to thinner epithelial and basement membrane layer and lower goblet and mast cell number than untreated asthmatic mice (p<0.001, p=0.001, p=0.005 and p=0.03 respectively). Neither epithelial and basement membrane thickness nor mast cell number was different among mice treated with etanercept and dexamethasone (p=0.38, p=0.79 and p=0.51 respectively). However, etanercept group was associated with thicker subepithelial muscle layer but lower goblet cell number (p<0.001 and p=0.04 respectively) than dexamethasone group. TNF antagonists and dexamethasone share many histopathological effects on asthmatic airway. Corticosteroids are more effective in decreasing smooth muscle mass while TNF antagonists in reducing goblet cell number. Therefore, further research is needed to assess the synergistic use of TNF antagonism and dexamethasone for more rational remodeling control.
    International immunopharmacology 09/2013; 17(3). DOI:10.1016/j.intimp.2013.08.021 · 2.47 Impact Factor
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    Immunological Reviews 07/2011; 242(1):5-9. DOI:10.1111/j.1600-065X.2011.01036.x · 10.12 Impact Factor
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