CCN1 在口腔扁平苔藓中的表达改变与角质形成细胞激活以及 IL-1β、ICAM1 和 CCL5 的上调有关。

Altered expression of CCN1 in oral lichen planus associated with keratinocyte activation and IL-1β, ICAM1, and CCL5 up-regulation.

机构信息

Department of Dermatology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Department of Oral Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

J Oral Pathol Med. 2020 Oct;49(9):920-925. doi: 10.1111/jop.13087. Epub 2020 Aug 14.

DOI:10.1111/jop.13087

PMID:32740993

Abstract

BACKGROUND

Emerging evidence indicates that CCN1 is a novel inflammation-regulated mediator involved in the pathogenesis of some immune-mediated inflammatory diseases. The objective of this study was to investigate the preliminary roles of CCN1 and its related cytokines IL-1β, CCL5, and ICAM1 in oral lichen planus (OLP).

METHODS

CCN1 expression levels in biopsies from OLP patients against normal oral mucosa (NOM) using immunohistochemistry (42 OLP vs 9 NOM) and RT-qPCR (20 OLP vs 20 NOM) were compared, respectively. The correlation of CCN1 and IL-1β, CCL5, and ICAM1 expression was examined by RT-qPCR in tissue samples and an in vitro cell culture system using keratinocyte HaCaT cells incubated with lipopolysaccharides.

RESULTS

Immunohistochemistry showed that CCN1 protein mainly expressed in the cytoplasm of epithelial keratinocytes of OLP. Consistently, RT-qPCR revealed that mRNA expression of CCN1 was increased in OLP compared with NOM (P < .05) and positively correlated with the high expression of IL-1β, ICAM1, and CCL5 (P < .001), respectively. Importantly, an in vitro study showed that keratinocyte proliferation significantly (P < .05) increased by CCN1 stimulation. Moreover, IL-1β, ICAM1, and CCL5 expression in keratinocytes stimulated by CCN1 was increased (P < .05), respectively.

CONCLUSIONS

This preliminary study for the first time reported that altered expression of CCN1 was associated with high expression of IL-1β, ICAM1, and CCL5 in OLP. And we demonstrated CCN1 promoted keratinocyte activation, as well as IL-1β, ICAM1, and CCL5 production in keratinocytes. Our data indicated that the potential role of CCN1 and its related cytokines was involved in the pathogenesis of OLP.

摘要

背景

新出现的证据表明，CCN1 是一种新的炎症调节介质，参与了一些免疫介导的炎症性疾病的发病机制。本研究的目的是探讨 CCN1 及其相关细胞因子 IL-1β、CCL5 和 ICAM1 在口腔扁平苔藓（OLP）中的初步作用。

方法

采用免疫组织化学法（42 例 OLP 与 9 例 NOM）和 RT-qPCR（20 例 OLP 与 20 例 NOM）分别比较了 OLP 患者活检组织中 CCN1 的表达水平。通过 RT-qPCR 检测组织样本和用脂多糖孵育的角质形成细胞 HaCaT 细胞体外细胞培养系统中 CCN1 与 IL-1β、CCL5 和 ICAM1 表达的相关性。

结果

免疫组织化学显示，CCN1 蛋白主要表达在 OLP 上皮角质形成细胞的细胞质中。同样，RT-qPCR 显示，与 NOM 相比，OLP 中 CCN1 的 mRNA 表达增加（P<.05），并与 IL-1β、ICAM1 和 CCL5 的高表达呈正相关（P<.001）。重要的是，体外研究表明，CCN1 刺激可显著（P<.05）增加角质形成细胞增殖。此外，CCN1 刺激的角质形成细胞中 IL-1β、ICAM1 和 CCL5 的表达增加（P<.05）。

结论

本初步研究首次报道，CCN1 的表达改变与 OLP 中 IL-1β、ICAM1 和 CCL5 的高表达有关。并且我们证明 CCN1 促进角质形成细胞激活以及角质形成细胞中 IL-1β、ICAM1 和 CCL5 的产生。我们的数据表明，CCN1 及其相关细胞因子的潜在作用可能参与了 OLP 的发病机制。