title: Multi-allergen challenge stimulates steriod-resistant airway inflammation via NF-κB-mediated IL-8 expression.
abstract: Neutrophilic airway inflammation associated with multiple allergens has been related to steroid-resistant asthma. However, most animal models use only one allergen, which cannot simulate asthma closely as seen in patients. To determine the mechanism of inflammatory process involved in this severe condition, BALB/c mice were repetitively challenged with the pooled extract of dust mite, ragweed, and Aspergillus species (DRA). We found that DRA increased interleukin (IL)-10 and TGF-β levels and neutrophil recruitment in bronchial alveolar lavage fluid. We also found that although dexamethasone suppressed the release of these two cytokines, mast cells recruitment, and mucus hypersecretion, it actually increased neutrophil infiltration and the level of keratinocyte-derived chemokine (mKC), a functional homolog of human IL-8. Treatment of human lung alveolar A549 cells with Der p1, an extract of house dust mite Dermatophagoides pteronyssinus, increased the expression of IL-8 and activity of NF-κB. The elevated IL-8 level was suppressed by BAY11-7082, a selective NF-κB inhibitor, but not by dexamethasone. These results suggest that increased IL-8 (mKC) levels may be involved in steroid-resistant neutrophilic airway inflammation through an NF-κB-dependent pathway.
authors: Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors: Renping
authors: R
authors: Liu
authors: Jinye
authors: J
authors: Bai
authors: Guoshun
authors: G
authors: Xu
authors: Lingling
authors: L
authors: Xuan
authors: Tianqi
authors: T
authors: Zhang
authors: Aiming
authors: A
authors: Meng
authors: Qi
authors: Q
authors: Hou
mesh_terms: D000818:Animals; D052179:Antigens, Plant / Q000276:immunology; D001230:Aspergillus / Q000276:immunology; D001249:Asthma / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D045744:Cell Line, Tumor; D040002:Dermatophagoides pteronyssinus / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology; D016753:Interleukin-10 / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism*; D020556:Neutrophil Infiltration / Q000276:immunology; D010936:Plant Extracts / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D052179:Antigens, Plant; D016209:Interleukin-8; D016328:NF-kappa B; D010936:Plant Extracts; D016212:Transforming Growth Factor beta; C433085:ragweed pollen; D016753:Interleukin-10; D003907:Dexamethasone