Reibman Joan, Hsu Yanshen, Chen Lung Chi, Bleck Bertram, Gordon Terry
Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA.
Am J Respir Cell Mol Biol. 2003 Jun;28(6):648-54. doi: 10.1165/rcmb.2002-0095OC.
The initiation and maintenance of airway immune responses in Th2 type allergic diseases such as asthma are dependent on the specific activation of local airway dendritic cells (DCs). The cytokine microenvironment, produced by local cells, influences the recruitment of specific subsets of immature DCs and their subsequent maturation. In the airway, DCs reside in close proximity to airway epithelial cells (AECs). We examined the ability of primary culture human bronchial epithelial cells (HBECs) to synthesize and secrete the recently described CC-chemokine, MIP-3alpha/CCL20. MIP-3alpha/CCL20 is the unique chemokine ligand for CCR6, a receptor with a restricted distribution. MIP-3alpha/CCL20 induces selective migration of DCs because CCR6 is expressed on some immature DCs but not on CD14+ DC precursors or mature DCs. HBECs were stimulated with pro-inflammatory cytokines tumor necrosis factor-alpha and interleukin (IL)-1beta or, because of their critical role in allergic diseases, IL-4 and IL-13. Cells were also exposed to small size-fractions of ambient particulate matter. Each of these stimuli induced MIP-3alpha/CCL20 gene and protein expression. Moreover, these agents upregulated mitogen-activated protein kinase pathways in HBECs. Inhibition of the ERK1/2 pathway or p38 reduced cytokine-induced MIP-3alpha/CCL20 expression. These data suggest a mechanism by which AEC may facilitate recruitment of DC subsets to the airway.
在诸如哮喘等Th2型过敏性疾病中，气道免疫反应的启动和维持依赖于局部气道树突状细胞（DCs）的特异性激活。局部细胞产生的细胞因子微环境会影响未成熟DCs特定亚群的募集及其随后的成熟。在气道中，DCs紧邻气道上皮细胞（AECs）。我们检测了原代培养的人支气管上皮细胞（HBECs）合成和分泌最近描述的CC趋化因子MIP-3α/CCL20的能力。MIP-3α/CCL20是CCR6的独特趋化因子配体，CCR6是一种分布受限的受体。MIP-3α/CCL20可诱导DCs的选择性迁移，因为CCR6在一些未成熟DCs上表达，但在CD14+DC前体或成熟DCs上不表达。用促炎细胞因子肿瘤坏死因子-α和白细胞介素（IL）-1β刺激HBECs，或者由于它们在过敏性疾病中的关键作用，用IL-4和IL-13刺激。细胞还暴露于环境颗粒物的小粒径部分。这些刺激中的每一种都诱导了MIP-3α/CCL20基因和蛋白表达。此外，这些因子上调了HBECs中的丝裂原活化蛋白激酶途径。抑制ERK1/2途径或p38可降低细胞因子诱导的MIP-3α/CCL20表达。这些数据提示了一种AEC可能促进DC亚群募集至气道的机制。
