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  • 1
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background Eosinophil infiltration is a hallmark of the inflammatory response in rhinitis and in nasal polypcsis.Objective We studied the effect of steroids and nedocromil sodium on eosinophil survival primed by epithelial cells from healthy (nasal mucosa) and inflamed (nasal polyp) respiratory tissue.Methods Blood eosinophils were incubated with increasing concentrations (10-11 10-5 M) of topical steroids (fiuticasone propionate, budesonide, triamcinolone acetonide and beclomethasone dipropionate) and/or nedocromil sodium prior to the addition of human epithelial cell conditioned media (HECM), eosinophil viability was measured and IC50 for each drug was calculated.Results All four steroids and nedocromil sodium caused a dose-related inhibition of HECM-induced eosinophil survival. The IC50 of steroids were lower in eosinophils primed by mucosa HECM than on those primed by polyp HECM (fluticasone, 4nM vs 114nM: budesonide, 21 nM vs 280 nM; triamcinolone, 7 nM vs 853 nM; and beclomethasone, 171 nM vs 181 nM). The combined inhibitory effect of 10-7M budesonide plus 10-5M nedocromil (43.8 ± 10.8%, P 〈 0.03) was significantly higher than budesonide (28.5 ± 9.2%) or nedocromil (16.7 ± 5.4%) alone and close to 10-5M budesonide (52.3 ± 11%). No differences were found in cytokine (IL-8, IL-6, GM-CSF, TNFα, IL-lβ and RANTES) concentrations between HECM from mucosa and polyps.Conclusion These results suggest that topical anti-inflammatory drugs may diminish airway eosinophilic infiltration by decreasing eosinophil viability, that nasal polyp epithelial cell secretions may induce steroid resistance in eosinophils, and that nedocromil sodium has additive effects with steroids.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Munksgaard International Publishers
    Allergy 59 (2004), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Inhaled and intranasal glucocorticoids are the most common and effective drugs for controlling symptoms and airway inflammation in respiratory diseases such as asthma, allergic rhinitis, and nasal polyposis. The last few years have seen a growing understanding of the mechanisms of glucocorticoid action and, in particular, the receptor that mediates glucocorticoid actions, the glucocorticoid receptor (GR). In this revision we present an update on the GR gene, the expression and regulation of its gene products, namely GRα and GRβ, as well as their alterations in pathological states. GRα is responsible for the induction and repression of target genes, it is expressed in virtually all human cells and tissues, and its expression is known to be downregulated by glucocorticoids. GRβ has been found to act as a dominant negative inhibitor of GRα-mediated transactivation in in vitro studies with transfected cells, but it does not appear to have a significant inhibitory effect on GRα-mediated transrepression. In addition, for most tissues the expression of GRβ, at least at the mRNA level, is extremely low compared with that of GRα. Some pro-inflammatory cytokines appear to upregulate the expression of GRβ, and increased GRβ expression has been reported in diseases associated with glucocorticoid resistance or insensitivity, such as bronchial asthma, nasal polyposis, and ulcerative colitis. However, the possible role of GRβ in modulating glucocorticoid sensitivity and/or resistance in vivo has been highly debated and it is not yet clear.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: We examined whether a decreased activity of nuclear factor(NF)-κB), a transcriptional regulator of cyclooxygenase-2 (COX-2), could account for down-regulation of COX-2 in nasal polyps of aspirin-sensitive asthmatics.Methods: Nasal polyps were obtained from 17 aspirin-intolerant asthma/rhinitis patients (AIAR; 7 men, mean age 48 ± 12 years) and 23 aspirin-tolerant asthma/rhinitis patients (ATAR; 12 men, mean age 65 ± 11 years). COX-2 mRNA expression was measured using semiquantitative reverse transcriptase competitive polymerase chain reaction (RT-PCR), and the results were expressed as mean ± standard error of 106 molecules of mRNA/µg of total RNA. NF-κB binding was measured with 32P-labeled oligonucleotides and electrophoretic mobility shift assay (EMSA), and the results were expressed as a percentage with respect to the mean EMSA obtained in 19 healthy nasal mucosa.Results: The mean levels of COX-2 mRNA expression (0.25 ± 0.06) and NF-κB activity (89 ± 13) in nasal polyps from AIAR were significantly lower than in polyps from ATAR (COX-2 = 1.58 ± 0.50, and NF-κB = 143 ± 12, P 〈 0.01 and P 〈 0.05, respectively). Levels of COX-2 mRNA and NF-κB activity in polyps from patients on corticosteroid therapy did not differ statistically from those who were not on this therapy before polypectomy.Conclusion: This study shows that the low expression of COX-2 mRNA in nasal polyps from aspirin-sensitive patients is associated with a down-regulation of NF-κB activity.
    Type of Medium: Electronic Resource
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