Correlation between β-defensin expression and induction profiles in gingival keratinocytes
Correlation between β-defensin expression and induction profiles in gingival keratinocytes
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DOI：
10.1016/j.molimm.2004.11.001
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发表时间：
2005-05-01
影响因子：
3.6
通讯作者：
Guthmiller, JM
中科院分区：
文献类型：
--
作者：
Joly, S;Organ, CC;Guthmiller, JM
人β -防御素是由上皮细胞产生的抗菌肽。迄今为止，已经描述了28种β -防御素，其中少数的表达被归类为构成型或诱导型。大多数研究使用有限数量的原代细胞培养或永生化细胞系来评估表达和调节。本研究的目的是定量评估人β -防御素，HBD-1， HBD-2和HBD-3在许多原发性牙龈角质形成细胞培养中的体外表达和诱导谱。用白细胞介素-1 β (IL-1 β)、白细胞介素-2 -6、白细胞介素-8、白细胞介素-12、肿瘤坏死因子α (tnf - α)、谷草干扰素（ifn - γ）或大肠杆菌脂多糖（LPS）刺激14例人培养的细胞，并采用逆转录(RT)-PCR分析。一部分培养物通过实时PCR进行定量评估。与HBD-2和HBD-3的表达量相比，HBD-1在基础水平（非刺激）的表达量最高且异质性最大，而HBD-2和HBD-3的表达量明显较低且均质。ifn - γ是HBD-1和HBD-3的主要诱导剂，而IL-1 β；和tnf - α是HBD-2的主要诱导剂。IL-2、IL-6和LPS有零星的诱导作用。多种细胞因子联合表达时出现协同表达。有趣的是，每种p -防御素的诱导电位与其基础表达直接相关。JAK2激酶（Janus激酶）抑制剂，下调ifn - γ诱导的HBD-1和HBD-3表达，提示JAK/信号转换器和转录激活因子（STAT）信号通路在其表达中的作用。上清液和细胞裂解液的HBD-2蛋白表达与mRNA表达平行。结果表明，p -防御素在牙龈角质形成细胞中的表达和诱导与其他组织相似。然而。诱导水平之间的巨大差异以及诱导与基础表达的相关性的新发现表明，这些先天反应元件可能在口腔疾病的易感性或抗性中发挥关键作用。(c) 2004 Elsevier Ltd.版权所有。
Human beta-defensins are antimicrobial peptides produced by epithelial cells. To date, 28 beta-defensins have been described and the expression of a select few has been classified as constitutive or inducible. Most studies have evaluated expression and regulation using a limited number of primary cell cultures or immortalized cell lines. The goal of this study was to quantitatively assess the in vitro expression and inducibility profiles of human beta-defensins, HBD-1, HBD-2, and HBD-3 across a number of primary gingival keratinocyte cultures. Cultured cells from 14 human subjects were stimulated with interleukin-1 beta (IL-1 beta), IL-2 IL-6, IL-8, IL-12, tumor necrosis factor alpha (TNF-alpha), gainnia interferon (IFN-gamma) or Escherichia coli lipopolysaccharide (LPS) and analyzed by reverse transcription (RT)-PCR. A subset of cultures were quantitatively assessed by real-time PCR. HBD-1 presented the highest and most heterogeneous expression at the basal level (non-stimulated) as compared to expression of HBD-2 and HBD-3, which was significantly lower and homogeneous. IFN-gamma was a primary inducer for HBD-1 and HBD-3, while IL-1 beta; and TNF-alpha were primary inducers for HBD-2. Sporadic induction was seen for IL-2, IL-6 and LPS. synergistic expression was seen when various cytokines were combined. Interestingly, the induction potential of each P-defensin was directly correlated to its basal expression. An inhibitor of JAK2 kinase (Janus kinase), down-regulated IFN-gamma-induced HBD-1 and HBD-3 expression, suggesting a role for the JAK/signal transducer and activator of transcription (STAT) signaling pathway in their expression. HBD-2 protein expression of supernatants and cell lysates paralleled mRNA expression. The results Suggest that P-defensin expression and induction in Gingival keratinocytes is similar to that seen in other tissue. However. the novel finding of considerable variation among induction levels and the correlation of the induction with basal expression suggests that these innate response elements may play a key role in susceptibility or resistance to disease in the oral cavity. (c) 2004 Elsevier Ltd. All rights reserved.