The Journal of allergy and clinical immunology
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J. Allergy Clin. Immunol. · Apr 2008
Corticosteroids enhance CD8+ T cell-mediated airway hyperresponsiveness and allergic inflammation by upregulating leukotriene B4 receptor 1.
Leukotriene B4 (LTB4) is a potent inflammatory lipid mediator that binds to LTB4 receptor 1 (BLT1). Ligation of BLT1 by LTB4 plays an important role in the recruitment of effector memory CD8+ T cells into the airways of sensitized and challenged mice. ⋯ Corticosteroids upregulate BLT1 on effector memory CD8+ T cells and related signaling pathways and potentiate allergic airway inflammation and AHR induced by these cells.
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J. Allergy Clin. Immunol. · Apr 2008
Comparative StudyEffective prevention and therapy of experimental allergic asthma using a GATA-3-specific DNAzyme.
Allergic bronchial asthma is a chronic inflammatory disease of the airways. The transcription factor GATA-3 was shown to play an important role in TH2 cell activation, but also in the regulation of other cell types involved in bronchial asthma including mast cells, eosinophils, and epithelial cells. DNAzymes represent a new class of antisense molecules that combines the specificity of DNA base pairing with an inherent RNA-cleaving enzymatic activity. ⋯ These results indicate that topical application of the GATA-3-specific DNAzyme is a promising novel approach for the treatment of allergic bronchial asthma.
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J. Allergy Clin. Immunol. · Apr 2008
Comment Letter Comparative StudyExtrapolating evidence beyond age groups.
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J. Allergy Clin. Immunol. · Mar 2008
ReviewThe role of histone deacetylases in asthma and allergic diseases.
Diverse cellular functions, including inflammatory gene expression, DNA repair, and cell proliferation, are regulated by histone acetylation. Transcriptional coactivators possess intrinsic histone acetyltransferase activity, and this activity drives inflammatory gene expression and the development of tolerance in macrophages. Eleven histone deacetylases (HDACs) act to regulate the expression of distinct subsets of inflammatory/immune genes. ⋯ However, the acetylation/deacetylation status of nonhistone proteins can also affect the overall expression pattern of inflammatory genes. HDAC2 expression and activity is reduced in lung macrophages, biopsy specimens, and blood cells from patients with severe asthma and smoking-induced asthma, as well as in patients with chronic obstructive pulmonary disease, perhaps accounting for the enhanced inflammation and reduced steroid responsiveness seen in these patients. Targeting specific enzymes involved in this process might lead to new therapeutic agents, particularly in situations in which current anti-inflammatory therapies are suboptimal.
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J. Allergy Clin. Immunol. · Mar 2008
Randomized Controlled TrialRapid corticosteroid effect on beta(2)-adrenergic airway and airway vascular reactivity in patients with mild asthma.
Long-term glucocorticoid therapy has been suggested to improve airway and airway vascular smooth muscle responsiveness to inhaled beta(2)-agonists in patients with asthma. ⋯ A single dose of an inhaled glucocorticoid restores beta(2)-adrenergic airway vasodilator responses in patients with mild asthma. The mechanism of this rapid glucocorticoid effect remains to be clarified.