Differential effects of α- and β-defensin on cytokine production by cultured human bronchial epithelial cells
Differential effects of α- and β-defensin on cytokine production by cultured human bronchial epithelial cells
复制标题
DOI：
10.1152/ajplung.00076.2004
复制
发表时间：
2005-03-01
影响因子：
4.9
通讯作者：
Kohno, S
中科院分区：
文献类型：
--
作者：
Sakamoto, N;Mukae, H;Kohno, S
防御素是一种富含半胱氨酸的阳离子抗菌肽，在先天免疫中起重要作用，并有助于调节宿主的适应性免疫。除了直接的抗微生物活性之外，最近报道了主要存在于肺中的嗜中性粒细胞中的α-防御素具有细胞毒性作用并诱导气道上皮细胞产生IL-8。虽然β-防御素在包括肺在内的各种组织的上皮细胞中表达，但没有关于其对气道上皮细胞中细胞因子合成的影响的报道。本研究的目的是确定α-和β-防御素对原代培养的人支气管上皮细胞（HBEC）中细胞因子产生，转录因子结合活性和细胞毒性的影响。我们使用人中性粒细胞肽-1（HNP-1; α-防御素）和人β-防御素-2（HBD-2）刺激HBEC。结果显示，HNP-1处理HBEC后，IL-8和IL-1 β mRNA表达呈剂量依赖性增加，IL-8蛋白分泌和NF-κ B DNA结合活性增加，而HBD-2处理HBEC后，IL-8和IL-1 β mRNA表达无明显变化。用>20 μ g/ml的HNP-1或>50 μ g/ml的HBD-2处理24小时对HBEC具有细胞毒性。这些结果表明，α-和β-防御素对气道上皮细胞的细胞因子合成有不同的影响，我们推测它们在炎症性肺疾病中发挥不同的作用。
Defensins are cysteine-rich cationic antimicrobial peptides that play an important role in innate immunity and are known to contribute to the regulation of host adaptive immunity. In addition to direct antimicrobial activities, it has been recently reported that alpha-defensins, mainly present in neutrophils in the lung, have a cytotoxic effect and induce IL-8 production from airway epithelial cells. Although beta-defensins are expressed in epithelial cells in various tissues, including lung, there are no reports of their effects on cytokine synthesis in airway epithelial cells. The aim of the present study was to determine the effects of both alpha- and beta-defensins on the cytokine production, transcription factor binding activity, and cytotoxicity in primary cultured human bronchial epithelial cells (HBECs). We used human neutrophil peptide-1 (HNP-1; alpha-defensin) and human beta-defensin-2 (HBD-2) to stimulate HBECs. The results showed that treatment of HBECs with HNP-1, but not HBD-2, increased IL-8 and IL-1beta mRNA expression in a dose-dependent manner and also enhanced IL-8 protein secretion and NF-kappaB DNA binding activity. The 24-h treatments with >20 mug/ml of HNP-1 or >50 mug/ml of HBD-2 were cytotoxic to HBECs. These results suggest that alpha- and beta-defensins have different effects on cytokine synthesis by airway epithelial cells, and we speculate that they play different roles in inflammatory lung diseases.