Hosokawa Yoshitaka, Hosokawa Ikuko, Shindo Satoru, Ozaki Kazumi, Matsuo Takashi
Department of Conservative Dentistry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Tokushima, Japan.
Cell Physiol Biochem. 2016;38(1):153-9. doi: 10.1159/000438617. Epub 2016 Jan 15.
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).
CCL20 and CCL11 productions from HPDLCs were monitored by ELISA. Western blot analysis was performed to detect phosphorylations of signal transduction molecules in HPDLCs.
IL-1β could induce both CCL11 and CCL20 productions in HPDLCs. IL-4 enhanced CCL11 productions from IL-1β-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-1β-stimulated HPDLCs. Akt and STAT6 inhibitors decreased CCL11 production, but enhanced CCL20 production in HPDLCs stimulated with IL-4 and IL-1β.
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.
背景/目的:白细胞介素-4(IL-4)是一种多功能细胞因子,与牙周疾病的病理状况相关。然而,IL-4是否能控制牙周病变中T细胞的迁移尚不确定。本研究的目的是检测IL-4对人牙周膜细胞(HPDLCs)中Th2型趋化因子CCL11以及与Th17细胞迁移相关的CCL20产生的影响。
采用酶联免疫吸附测定法(ELISA)监测HPDLCs中CCL20和CCL11的产生。进行蛋白质免疫印迹分析以检测HPDLCs中信号转导分子的磷酸化情况。
IL-1β可诱导HPDLCs产生CCL11和CCL20。IL-4增强了IL-1β刺激的HPDLCs中CCL11的产生,尽管IL-4抑制了CCL20的产生。蛋白质免疫印迹分析表明,在IL-4/IL-1β刺激的HPDLCs中,蛋白激酶B(Akt)和信号转导及转录激活因子(STAT)6通路被高度激活。Akt和STAT6抑制剂降低了CCL11的产生,但增强了IL-4和IL-1β刺激的HPDLCs中CCL20的产生。
这些结果表明,IL-4增强了牙周病变中Th2细胞的迁移,从而诱导HPDLCs产生CCL11。另一方面,IL-4抑制了牙周病组织中Th17细胞的聚集,从而抑制CCL20的产生。因此,IL-4与牙周疾病的发病机制呈正相关,可控制牙周病变中趋化因子的产生。