The allergen Der p1 induces NF-kappaB activation through interference with IkappaB alpha function in asthmatic bronchial epithelial cells.
Asthma is an inflammatory disease of the airways due to an interaction between genetic and environmental factors, and allergy represents the most important predisposing trait. Here, we investigated why and how the allergen most often implicated in the pathogenesis of asthma and other allergic diseases causes the expression of the genes for proinflammatory cytokines in airway epithelium. We found that Der p1 promotes activation of transcriptional factor NF-kappaB by interference with the function of its cytoplasmic inhibitor IkappaB alpha. This is the first report on the effect of an allergen on transcriptional factors. Our results improve the understanding of the mechanisms involved in allergic diseases and suggest potential therapeutic utility of NF-kappaB blockers.
Stacey
M A
MA
Institute of Experimental Medicine, Milan, Italy.
Sun
G
G
Vassalli
G
G
Marini
M
M
Bellini
A
A
Mattoli
S
S
D000328:Adult; D039741:Antigens, Dermatophagoides; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000503:physiopathology*; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D004848:Epithelium / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051841:Transcription Factor RelB; D014157:Transcription Factors; D014158:Transcription, Genetic
D039741:Antigens, Dermatophagoides; D018946:Chemokine CCL5; D004268:DNA-Binding Proteins; D006023:Glycoproteins; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; C497593:RELB protein, human; D014157:Transcription Factors; D051841:Transcription Factor RelB; D016178:Granulocyte-Macrophage Colony-Stimulating Factor