Fluticasone reduces IL-6 and IL-8 production of cystic fibrosis bronchial epithelial cells via IKK-β kinase pathway
Fluticasone reduces IL-6 and IL-8 production of cystic fibrosis bronchial epithelial cells via IKK-β kinase pathway
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DOI：
10.1183/09031936.03.00031803
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发表时间：
2003-04-01
影响因子：
24.3
通讯作者：
Jacquot, J
中科院分区：
文献类型：
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作者：
Escotte, S;Tabary, O;Jacquot, J
吸入丙酸氟替卡松(FP)被广泛用于减轻慢性阻塞性肺疾病患者的肺部炎症，但FP对囊性纤维化(CF)患者呼吸道上皮细胞的潜在作用尚不清楚。在CF病中，通过过度激活核因子(NF)-kappaB和增加促炎症细胞因子的产生而发生非调节性炎症反应。为了确定FP是否通过NF-kappaB减少支气管上皮细胞中细胞因子的产生，作者研究了未刺激和铜绿假单胞菌脂多糖(LPS)刺激的依赖于NF-kappaB的白细胞介素6(IL)-6、IL-8和RANTES的产生。结果表明，一定浓度的FP(10(-8)M)可抑制非CF型和CIF型支气管腺上皮细胞结构性和铜绿假单胞菌诱导的IL-6和IL-8产生。有趣的是，经FP处理后，两种IkappaB激酶(IKK)-α/β的表达、胞内IkappaB-β抑制剂的降解以及核因子-kappaB脱氧核糖核酸结合活性均显著降低。作者发现，丙酸氟替卡松通过阻断导致支气管上皮细胞IkappaB-α/βKMA水平降低的信号转导而发挥抗炎作用。尤其是对囊性纤维化患者的支气管上皮细胞中已知升高的IkappaB-β激酶的强烈影响。
Inhaled fluticasone propionate (FP) is widely used to reduce pulmonary inflammation in chronic obstructive pulmonary disease, but the potential effects of FP on airway epithelial cells from patients with cystic fibrosis (CF) are unknown. In CF disease, a nonregulated inflammatory lung response occurs through exaggerated nuclear factor (NF)-kappaB activation and elevated pro-inflammatory cytokines production by airway epithelial cells.To determine whether FP reduces cytokine production in bronchial epithelial cells via NF-kappaB, the authors investigated the nonstimulated and the Pseudomonas aeruginosa lipopolysaccharide (LPS) stimulated production of NF-kappaB-dependent interleukin (IL)-6, IL-8 and RANTES (regulated on activation, T-cell expressed and secreted) along with the activation of NF-kappaB in non-CF and CF human bronchial gland epithelial cells.It was demonstrated that a relevant concentration of FP (10(-8) M) inhibited constitutive and P. aeruginosa LPS-induced IL-6 and IL-8 production of non-CF and CIF bronchial epithelial cells. Interestingly, the expression of two IkappaB kinases (IKK)-alpha/beta, the degradation of cytosolic IkappaB-beta inhibitor and the NF-kappaB deoxyribonucleic acid binding activity were markedly reduced after FP treatment in both CF and non-CF bronchial epithelial cells.It was shown by the authors that fluticasone propionate exerts an anti-inflammatory effect by blocking a signal transduction leading to a reduced level of IkappaB-alpha/beta kmases in bronchial epithelial cells. In particular the strong effect on the IkappaB-beta kinase, which is known to be elevated in bronchial epithelial cells in cystic fibrosis patients, was observed.