白细胞介素-27调节肿瘤坏死因子-α刺激的人口腔上皮细胞中的趋化因子产生。

IL-27 Modulates Chemokine Production in TNF-α -Stimulated Human Oral Epithelial Cells.

作者信息

Hosokawa Yoshitaka, Hosokawa Ikuko, Ozaki Kazumi, Matsuo Takashi

机构信息

Department of Conservative Dentistry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.

Department of Oral Health Care Promotion, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.

出版信息

Cell Physiol Biochem. 2017;43(3):1198-1206. doi: 10.1159/000481760. Epub 2017 Oct 5.

DOI:10.1159/000481760

PMID:28977795

Abstract

BACKGROUND/AIMS: Interleukin-27 (IL-27) is a cytokine which belongs to the IL-12 family. However, the role of IL-27 in the pathogenesis of periodontal disease is uncertain. The aim of this study was to examine the effect of IL-27 on chemokine production in TNF-α-stimulated human oral epithelial cells (TR146).

METHODS

We measured chemokine production in TR146 by ELISA. We used western blot analysis to detect the phosphorylation levels of signal transduction molecules, including STAT1 and STAT3 in TR146. We used inhibitors to examine the role of STAT1 and STAT3 activation.

RESULTS

IL-27 increased CXCR3 ligands production in TNF-α-stimulated TR146. Meanwhile, IL-27 suppressed IL-8 and CCL20 production induced by TNF-α. STAT1 phosphorylation level in IL-27 and TNF-α-stimulated TR146 was enhanced in comparison to TNF-α-stimulated TR146. STAT3 phosphorylation level in IL-27-treated TR146 did not change by TNF-α. Both STAT1 inhibitor and STAT3 inhibitor decreased CXCR3 ligands production. STAT1 inhibitor overrode the inhibitory effect of IL-27 on IL-8 and CCL20 production in TNF-α-stimulated TR146. Meanwhile, STAT3 inhibitor did not modulate IL-8 and CCL20 production.

CONCLUSION

IL-27 might control leukocyte migration in periodontal lesion by modulating chemokine production from epithelial cells.

摘要

背景/目的：白细胞介素-27（IL-27）是一种属于IL-12家族的细胞因子。然而，IL-27在牙周病发病机制中的作用尚不确定。本研究旨在探讨IL-27对肿瘤坏死因子-α（TNF-α）刺激的人口腔上皮细胞（TR146）趋化因子产生的影响。

方法

我们通过酶联免疫吸附测定法（ELISA）测量TR146中趋化因子的产生。我们使用蛋白质印迹分析来检测TR146中信号转导分子（包括信号转导和转录激活因子1（STAT1）和信号转导和转录激活因子3（STAT3））的磷酸化水平。我们使用抑制剂来研究STAT1和STAT3激活的作用。

结果

IL-27增加了TNF-α刺激的TR146中CXC趋化因子受体3（CXCR3）配体的产生。同时，IL-27抑制了TNF-α诱导的白细胞介素-8（IL-8）和CC趋化因子配体20（CCL20）的产生。与TNF-α刺激的TR146相比，IL-27和TNF-α刺激的TR146中STAT1磷酸化水平增强。TNF-α未改变IL-27处理的TR146中STAT3磷酸化水平。STAT1抑制剂和STAT3抑制剂均降低了CXCR3配体的产生。STAT1抑制剂克服了IL-27对TNF-α刺激的TR146中IL-8和CCL20产生的抑制作用。同时，STAT3抑制剂未调节IL-8和CCL20的产生。