CCL20 is an inducible product of human airway epithelia with innate immune properties
CCL20 is an inducible product of human airway epithelia with innate immune properties
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DOI：
10.1165/rcmb.2002-0272oc
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发表时间：
2003-11-01
影响因子：
6.4
通讯作者：
McCray, PB
中科院分区：
文献类型：
--
作者：
Starner, TD;Barker, CK;McCray, PB
趋化因子配体20（CCL 20）和人β-防御素（HBD）具有相同的结构和功能特性，包括反平行β-折叠片核心结构、电荷分布和通过高选择性CCR 6受体向适应性免疫细胞发出信号。由于它们的相似性，我们假设除了其已知的适应性免疫信号传导功能外，CCL 20还具有抗微生物特性并参与肺先天免疫。我们发现，原代培养的人气道上皮细胞和培养的胎肺外植体表达CCL 20 mRNA。IL-1 β和TNF-α可显著诱导CCL 20转录本的表达，地塞米松可抑制CCL 20转录本的表达。气道上皮细胞的原代培养物在顶部和基底外侧均分泌CCL 20，并且在IL-1 β刺激下CCL 20丰度增加超过30倍，在气道表面液体中达到167 ng/ml的估计浓度。囊性纤维化患者支气管肺泡灌洗液中CCL 20的丰度比健康志愿者的支气管肺泡灌洗液高出近90倍。有趣的是，CCL 20表现出盐敏感性抗微生物活性，主要针对低μ g/ml浓度的革兰氏阴性菌。此外，来自IL-1 β刺激的人气道上皮原代培养物的顶端冲洗液比未刺激的对照具有显著更高的抗菌活性。CCL 20快速透化细菌膜，其时间过程介于HBD-2和HBD-3之间。因此，CCL 20是一种具有先天性和适应性免疫特性的双功能肽，其由炎症介质调节，由气道上皮细胞表达，并在囊性纤维化气道分泌物中增加。
Chemokine ligand 20 (CCL20) and human beta-defensins (HBDs) share structural and functional properties, including antiparallel beta-pleated sheet core structures, charge distribution, and signaling to adaptive immune cells via the highly selective CCR6 receptor. Because of their similarities, we hypothesized that in addition to its known adaptive immune signaling functions, CCL20 has antimicrobial properties and participates in pulmonary innate immunity. We found that primary cultures of human airway epithelial and cultured fetal lung explants expressed CCL20 mRNA. Expression of CCL20 transcripts were significantly induced by interleukin (IL)-1beta and tumor necrosis factor-alpha, and inhibited by dexamethasone. Primary cultures of airway epithelia secreted CCL20 both apically and basolaterally, and CCL20 abundance was increased over 30-fold with IL-1beta stimulation, achieving an estimated concentration of 167 ng/ml in airway surface liquid. CCL20 abundance in bronchoalveolar lavage fluid from patients with cystic fibrosis was nearly 90-fold higher compared with bronchoalveolar lavage fluid from healthy volunteers. Interestingly, CCL20 exhibited salt-sensitive antimicrobial activity, mainly against Gram-negative bacteria in low mug/ml concentrations. Additionally, apical washings from IL-1beta-stimulated primary cultures of human airway epithelia had significantly more antimicrobial activity than unstimulated controls. CCL20 rapidly permeabilized bacterial membranes with a time course intermediate to HBD-2 and HBD-3. Thus, CCL20 is a bi-functional peptide with both innate and adaptive immune properties that is regulated by inflammatory mediators, expressed by airway epithelia, and increased in cystic fibrosis airway secretions.