Anti-inflammatory effects of azithromycin in cystic fibrosis airway epithelial cells
Anti-inflammatory effects of azithromycin in cystic fibrosis airway epithelial cells
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DOI：
10.1016/j.bbrc.2006.09.132
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发表时间：
2006-12-01
影响因子：
3.1
通讯作者：
Melotti, Paola
中科院分区：
文献类型：
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作者：
Cigana, Cristina;Nicolis, Elena;Melotti, Paola
本研究旨在探讨阿奇霉素（azithromycin，AZM）抗炎作用的分子机制。研究了囊性纤维化（CF）和同基因非CF气道上皮细胞系中IL-8表达和两种关键促炎转录因子（TF）NF-κ B和AP-1的DNA结合活性。AZM使CF细胞中IL-8 mRNA和蛋白表达降低约40%（n = 9，p = 0.02和n = 4，p = 0.00011），达到非CF细胞的水平。在AZM存在下，我们发现NF-κ B和AP-1 DNA结合分别减少约50%和70%（n = 3，p = 0.01和n = 3，p = 0.0017），导致非CF细胞水平。NF-κ B和AP-1在调节IL-8启动子转录活性中的相关性通过基因报告基因测定得到证实（17 = 4，p = 8.54 x 10（-7）和n = 4，p = 6.45 x 10（-6））。我们的数据支持AZM在CF细胞中的抗炎作用，表明抑制促炎基因的转录是可能的机制，从而为可能使用特异性TF抑制剂进行治疗提供了理论基础。(c)2006年爱思唯尔公司All rights reserved.
We aimed at identifying molecular mechanisms for anti-inflammatory effects of azithromycin (AZM) suggested by clinical evidences. IL-8 expression and DNA binding activity of two key pro-inflammatory transcription factors (TF), NF-kappa B and AP-1, were investigated in cystic fibrosis (CF) and isogenic non-CF airway epithelial cell lines. AZM reduced about 40% of IL-8 mRNA and protein expression (n = 9, p = 0.02, and n = 4, p = 0.00011) in CF cells reaching the levels of non-CF cells. In the presence of AZM we found about 50% and 70% reduction of NF-kappa B and AP-1 DNA binding, respectively (n = 3, p = 0.01, and n = 3, p = 0.0017), leading to levels of non-CF cells. The relevance of NF-kappa B and AP-1 in regulating IL-8 promoter transcriptional activity was demonstrated by gene reporter assays (17 = 4, p = 8.54 x 10(-7), and n = 4,p = 6.45 x 10(-6)). Our data support the anti-inflammatory effects of AZM in CF cells, indicating inhibition of transcription of pro-inflammatory genes as possible mechanism, thus providing a rationale for the possible use of specific TF inhibitors for therapy. (c) 2006 Elsevier Inc. All rights reserved.