Impaired Interleukin-8 Chemokine Secretion by Staphylococcus aureus-Activated Epithelium and T-Cell Chemotaxis in Cystic Fibrosis
Impaired Interleukin-8 Chemokine Secretion by Staphylococcus aureus-Activated Epithelium and T-Cell Chemotaxis in Cystic Fibrosis
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DOI：
10.1165/rcmb.2008-0021oc
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发表时间：
2010-06-01
影响因子：
6.4
通讯作者：
Gangloff, Sophie Catherine
中科院分区：
文献类型：
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作者：
Al Alam, Denise;Deslee, Gaetan;Gangloff, Sophie Catherine
金黄色葡萄球菌经常从囊性纤维化患者的肺中分离出来。肺部感染金黄色葡萄球菌后，呼吸道上皮细胞(AEC)产生高水平的趋化因子，增强T细胞的趋化能力。虽然CF患者呼吸道和支气管肺泡灌洗液中的淋巴细胞数量增加，但其聚集的机制和金黄色葡萄球菌在这一过程中的作用尚不清楚。本研究探讨了早期金黄色葡萄球菌对CF上皮细胞分泌趋化因子和CFT细胞趋化作用的影响。在细胞培养模型中培养CF型和非CF型AEC，并用金黄色葡萄球菌顶端刺激。培养上清液定量检测趋化因子的分泌，并检测T细胞的趋化能力。CFAEC分泌IL-8、Groα、MIG、MIP-313和MCP-1的数量明显多于非CFEC。金黄色葡萄球菌与上皮细胞的相互作用增加了非CF细胞的趋化因子的产生，但对CF细胞没有影响。慢性萎缩性胃炎患者T细胞的趋化性明显强于非慢性萎缩性胃炎患者。与非CFT细胞相比，CFT细胞表达CXCR1的细胞更多。在我们的实验条件下，抑制IL-8或其受体CXCR1会导致T细胞趋化性显著降低(最高可达80%)。提示IL-8及其受体CXCR1在CFT细胞的趋化作用中起关键作用，可作为治疗CFT的靶点。
Staphylococcus aureus is frequently isolated from lungs of patients with cystic fibrosis (CF). Upon lung infection with S. aureus, airway epithelial cells (AEC) produce high levels of chemokines that enhance T-cell chemotaxis. Although the number of lymphocytes is increased in the airways and bronchoalveolar lavage fluid of patients with CF, the mechanisms responsible for their accumulation and the role of S. aureus in this process are largely unknown. This study investigated early S. aureus impact on chemokine secretion by CF epithelial cells and chemotaxis of CF T cells. CF and non-CF AEC were grown in a cell culture model and apically stimulated with S. aureus. Supernatants were quantified for chemokine secretions and assayed for T-cell chemotaxis. CF AEC secreted constitutively larger amounts of IL-8, GRO alpha, MIG, MIP-313, and MCP-1 than non-CF epithelial cells. S. aureus interaction with epithelial cells increased chemokine production by non-CF cells but had no effect on CF cells. Chemotaxis of T cells derived from patients with CF was greater than that of T cells from subjects without CF. Moreover, there were more CF T cells expressing CXCR1 as compared with non-CF T cells. Under our experimental conditions, inhibition of IL-8 or its receptor CXCR1 resulted in a considerable decrease in T-cell chemotaxis (up to 80%). These data suggest that IL-8 and its receptor CXCR1 are key players in the chemotaxis of CF T cells and could be used as targets to develop therapies for CF.