TITLE

Relative corticosteroid insensitivity of alveolar macrophages in severe asthma compared with non-severe asthma

AUTHOR(S)
Bhavsar, P.; Hew, M.; Khorasani, N.; Torrego, A.; Barnes, P. J.; Adcock, I.; Chung, K. F.
PUB. DATE
September 2008
SOURCE
Thorax;Sep2008, Vol. 63 Issue 9, p784
SOURCE TYPE
Academic Journal
DOC. TYPE
journal article
ABSTRACT
Background: About 5-10% of patients with asthma suffer from poorly controlled disease despite corticosteroid (CS) treatment, which may indicate the presence of CS insensitivity. A study was undertaken to determine whether relative CS insensitivity is present in alveolar macrophages from patients with severe asthma and its association with p38 mitogen-activated protein kinase (MAPK) activation and MAPK phosphatase-1 (MKP-1).Methods: Fibreoptic bronchoscopy and bronchoalveolar lavage (BAL) were performed in 20 patients with severe asthma and 19 with non-severe asthma and, for comparison, in 14 normal volunteers. Alveolar macrophages were exposed to lipopolysaccharide (LPS, 10 mug/ml) and dexamethasone (10(-8) and 10(-6) M). Supernatants were assayed for cytokines using an ELISA-based method. p38 MAPK activity and MKP-1 messenger RNA expression were assayed in cell extracts.Results: The inhibition of LPS-induced interleukin (IL)1beta, IL6, IL8, monocyte chemotactic protein (MCP)-1 and macrophage inflammatory protein (MIP)-1alpha release by dexamethasone (10(-6) M) was significantly less in macrophages from patients with severe asthma than in macrophages from patients with non-severe asthma. There was increased p38 MAPK activation in macrophages from patients with severe asthma. MKP-1 expression induced by dexamethasone and LPS, expressed as a ratio of LPS-induced expression, was reduced in severe asthma.Conclusion: Alveolar macrophages from patients with severe asthma demonstrate CS insensitivity associated with increased p38 MAPK activation that may result from impaired inducibility of MKP-1.
ACCESSION #
34395943

 

Related Articles

  • Corticosteroid suppression of lipoxin A4 and leukotreine B4 from alveolar macrophages in severe asthma. Bhavsar, Pankaj K.; Levy, Bruce D.; Hew, Mark J.; Pfeffer, Michael A.; Kazani, Shamsah; Israel, Elliot; Kian Fan Chung // Respiratory Research;2010, Vol. 11, p71 

    Background: An imbalance in the generation of pro-inflammatory leukotrienes, and counter-regulatory lipoxins is present in severe asthma. We measured leukotriene LTB4 (LTB4), and lipoxin A4 (LXA4) production by alveolar macrophages (AMs) and studied the impact of corticosteroids. Methods: AMs...

  • In this Issue.  // Mucosal Immunology (1933-0219);Sep2014, Vol. 7 Issue 5, p1021 

    The article presents several abstracts on topics related to mucosal immunology including the association macrophage activation and fungal infections, HIV inhibition of alveolar macrophage function, and nitrative stress and asthma.

  • Restoration of Corticosteroid Sensitivity by p38 Mitogen Activated Protein Kinase Inhibition in Peripheral Blood Mononuclear Cells from Severe Asthma. Mercado, Nicolas; Hakim, Amir; Kobayashi, Yoshiki; Meah, Sally; Usmani, Omar S.; Chung, Kian Fan; Barnes, Peter J.; Ito, Kazuhiro // PLoS ONE;Jul2012, Vol. 7 Issue 7, p1 

    Background: Severe asthma accounts for a small number of asthmatics but represents a disproportionate cost to health care systems. The underlying mechanism in severe asthma remains unknown but several mechanisms are likely to be involved because of a very heterogeneous profile. We investigated...

  • Is there more than one inflammatory phenotype is asthma? O'Donnell, R. A.; Frew, A. J. // Thorax;Jul2002, Vol. 57 Issue 7, p566 

    The article discusses whether there is more than one inflammatory phenotype in asthma. But there are some problems in asthma investigations. Most asthmatic patients recruited to these studies either had severe disease or were on some form of corticosteroid therapy, raising concerns about...

  • Don't wait to inhale. Lee, Janet // Self;Apr2000, Vol. 22 Issue 4, p84 

    Presents treatments for asthma. Corticosteroids, for severe asthma; Anti-leukotrienes, for moderate asthma; Natural remedies for the disease.

  • Clinical aspects of asthma.  // Thorax;Dec2006 Supplement 2, Vol. 61, pii125 

    The article presents abstracts of medical research related to clinical aspects of asthma. They include "Evidence-based Asthma Training Improves Asthma," "Severe Asthma Is Associated With Tidal Breathing Close to Residual Volume," and "Adrenal Function of Patients With Bronchiectasis and Asthma...

  • Smoking in Asthma Is Associated with Elevated Levels of Corticosteroid Resistant Sputum Cytokines—An Exploratory Study. Spears, Mark; McSharry, Charles; Chaudhuri, Rekha; Weir, Christopher J.; de Wet, Carl; Thomson, Neil C. // PLoS ONE;Aug2013, Vol. 8 Issue 8, p1 

    Background: Current cigarette smoking is associated with reduced acute responses to corticosteroids and worse clinical outcomes in stable chronic asthma. The mechanism by which current smoking promotes this altered behavior is currently unclear. Whilst cytokines can induce corticosteroid...

  • Obesity Increases Airway Hyperresponsiveness via the TNF-α Pathway and Treating Obesity Induces Recovery. Kim, Joo Young; Sohn, Jung-Ho; Lee, Jae-Hyun; Park, Jung-Won // PLoS ONE;Feb2015, Vol. 10 Issue 2, p1 

    Obesity is a known risk factor for allergic asthma. It has been recognized as a key player in the pathogenesis of several inflammatory disorders via activation of macrophages, which is also vital to the development of allergic asthma. We investigated the mechanism of obesity-related asthma and...

  • Inhaled corticosteroids as combination therapy with β-adrenergic agonists in airways disease: present and future. Kian Fan Chung; Caramori, Gaetano; Adcock, Ian M. // European Journal of Clinical Pharmacology;Sep2009, Vol. 65 Issue 9, p853 

    Inhaled corticosteroid (ICS) therapy in combination with long-acting β-adrenergic agonists represents the most important treatment for chronic airways diseases such as asthma and chronic obstructive pulmonary disease (COPD). ICS therapy forms the basis for treatment of asthma of all...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sign out of this library

Other Topics