IL-4 Modulates CCL11 and CCL20 Productions from IL-1β-Stimulated Human Periodontal Ligament Cells
IL-4 Modulates CCL11 and CCL20 Productions from IL-1β-Stimulated Human Periodontal Ligament Cells
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DOI：
10.1159/000438617
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发表时间：
2016-01-01
影响因子：
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通讯作者：
Matsuo, Takashi
中科院分区：
文献类型：
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作者：
Hosokawa, Yoshitaka;Hosokawa, Ikuko;Matsuo, Takashi
背景与目的：IL-4是一种多功能细胞因子，与牙周病的病理状态密切相关。然而，IL-4是否能控制牙周病变中T细胞的迁移尚不确定。本研究旨在观察IL-4对人牙周膜细胞（HPDLCs）分泌的Th 2型趋化因子CCL 11和与Th 17细胞迁移相关的CCL 20的影响。方法：采用ELISA法检测人牙周膜细胞产生CCL 20和CCL 11的能力。Western blot检测HPDLCs中信号转导分子的磷酸化。结果：IL-1 β可诱导HPDLCs产生CCL 11和CCL 20。IL-4促进IL-1 β刺激的HPDLCs产生CCL 11，但IL-4抑制CCL 20的产生。Western blot分析显示，IL-4/IL-1 β刺激后，HPDLCs蛋白激酶B（Akt）和信号转导及转录激活因子（STAT）6通路高度激活。Akt和STAT 6抑制剂降低了用IL-4和IL-1 β刺激的HPDLCs中CCL 11的产生，但增强了CCL 20的产生。结论：IL-4可促进Th 2细胞在牙周病损区的迁移，诱导牙周病损区HPDLCs产生CCL 11。另一方面，IL-4抑制Th 17细胞在牙周病组织中的积聚，从而抑制CCL 20的产生。因此，IL-4与牙周病的发病机制正相关，可以控制牙周病变中趋化因子的产生。(C)2016作者（S）
Background/Aims: IL-4 is a multifunctional cytokine that is related with the pathological conditions of periodontal disease. However, it is uncertain whether IL-4 could control T cells migration in periodontal lesions. The aim of this study was to examine the effects of IL-4 on CCL11, which is a Th2-type chemokine, and CCL20, which is related with Th17 cells migration, productions from human periodontal ligament cells (HPDLCs). Methods: CCL20 and CCL11 productions from HPDLCs were monitored by ELISA. Western blot analysis was performed to detect phosphorylations of signal transduction molecules in HPDLCs. Results: IL-1 beta could induce both CCL11 and CCL20 productions in HPDLCs. IL-4 enhanced CCL11 productions from IL-1 beta-stimulated HPDLCs, though IL-4 inhibited CCL20 production. Western blot analysis showed that protein kinase B (Akt) and signal transducer and activator of transcription (STAT) 6 pathways were highly activated in IL-4/IL-1 beta-stimulated HPDLCs. Akt and STAT6 inhibitors decreased CCL11 production, but enhanced CCL20 production in HPDLCs stimulated with IL-4 and IL-1 beta. Conclusions: These results mean that IL-4 enhanced Th2 cells migration in periodontal lesion to induce CCL11 production from HPDLCs. On the other hand, IL-4 inhibits Th17 cells accumulation in periodontally diseased tissues to inhibit CCL20 production. Therefore, IL-4 is positively related with the pathogenesis of periodontal disease to control chemokine productions in periodontal lesions. (C) 2016 The Author(s)