The non-proteolytic house dust mite allergen Der p 2 induce NF-κB and MAPK dependent activation of bronchial epithelial cells
The non-proteolytic house dust mite allergen Der p 2 induce NF-κB and MAPK dependent activation of bronchial epithelial cells
复制标题
DOI：
10.1111/j.1365-2222.2009.03284.x
复制
发表时间：
2009-08-01
影响因子：
6.1
通讯作者：
Bucht, A.
中科院分区：
文献类型：
--
作者：
Osterlund, C.;Gronlund, H.;Bucht, A.
背景屋尘螨（HDM）是众所周知的室内空气过敏原的来源，并可引起过敏性气道疾病。已知一些蛋白水解的HDM过敏原可激活呼吸道上皮细胞产生促炎介质，而对非蛋白水解的HDM过敏原的这种活性了解有限。激活呼吸道上皮细胞产生参与哮喘发病机制的介质，并阐明这种激活的机制。将支气管上皮细胞系BEAS-2B、正常人支气管上皮（NHBE）细胞和肺泡上皮细胞系A549暴露于重组Der p 2。暴露后，我们分析了一组可溶性介质和细胞粘附受体参与哮喘发病机制，促进招聘，生存和结合的炎症细胞。核因子（NF）-κ B和丝裂原活化蛋白激酶（MAPKs）的参与进行了研究，使用特定的inhibitors.ResultsDer p 2激活支气管BEAS-2B和NHBE细胞，但不是肺泡A549细胞。在BEAS-2B细胞中，Der p 2诱导粒细胞-巨噬细胞集落刺激因子、IL-6、IL-8、单核细胞趋化蛋白-1和巨噬细胞炎性蛋白-3 α的mRNA水平和蛋白分泌的剂量依赖性上调。细胞间粘附分子（ICAM）-1的分泌和表面表达也上调，这与单核细胞与上皮细胞的粘附增加有关。细胞因子和趋化因子的释放调节NF-κ B B和MAPK激活以不同的方式，而ICAM-1的表达是完全依赖于NF-κ B activation.ConclusionThese结果表明，Der p 2激活呼吸道上皮细胞，这表明，这种非蛋白水解过敏原，除了其免疫原性，可以加重呼吸道疾病的肺上皮细胞的恶性肿瘤样激活。
P>BackgroundHouse dust mites (HDM) are well-known as a source of indoor aeroallergens and for causing allergic airway diseases. Some proteolytic HDM allergens are known to activate respiratory epithelial cells to produce pro-inflammatory mediators, while there is limited knowledge regarding such activity among non-proteolytic HDM allergens.ObjectiveTo investigate whether Der p 2, a major non-proteolytic allergen of Dermatophagoides pteronyssinus, activates respiratory epithelial cells to produce mediators involved in asthma pathogenesis and to elucidate the mechanism of such activation.MethodsThe human bronchial epithelial cell line BEAS-2B, normal human bronchial epithelial (NHBE) cells and the alveolar epithelial cell line A549 were exposed to recombinant Der p 2. Following exposure, we analysed a panel of soluble mediators and cell adhesion receptors involved in asthma pathogenesis by promoting recruitment, survival and binding of inflammatory cells. The involvement of nuclear factor (NF)-kappa B and mitogen-activated protein kinases (MAPKs) was studied using specific inhibitors.ResultsDer p 2 activated bronchial BEAS-2B and NHBE cells, but not alveolar A549 cells. In BEAS-2B cells Der p 2 induced dose-dependent up-regulation in both mRNA level and protein secretion of granulocyte-macrophage colony-stimulating factor, IL-6, IL-8, monocyte-chemotactic protein-1 and macrophage inflammatory protein-3 alpha. Secretion as well as surface expression of intercellular adhesion molecule (ICAM)-1 was also up-regulated, which was associated with increased adhesion of monocytes to the epithelial cells. The release of cytokines and chemokines was regulated by NF-kappa B and MAPK activation in different ways, while expression of ICAM-1 was solely dependent on NF-kappa B activation.ConclusionThese results show that Der p 2 activates respiratory epithelial cells, indicating that this non-proteolytic allergen, in addition to its immunogenic properties, can aggravate respiratory airway disease by adjuvant-like activation of the lung epithelium.