Cyr61上调人角质形成细胞表达IL-36α的实验研究  

Cyr61 up-regulates the expression of IL-36 in human keratinocytes

作　　者：袁华英[1] 张洁[2] 余韦臻 李会丹[2] 翟天航 徐慧[1] 

机构地区：[1]上海交通大学医学院附属第九人民医院皮肤科,上海200011 [2]上海交通大学医学院上海市免疫学研究所,上海200025

出　　处：《现代免疫学》2017年第3期212-217,共6页Current Immunology

基　　金：上海交通大学医学院附属第九人民医院南北融合基金;上海市自然科学基金项目(16ZR1419200)

摘　　要：银屑病是多种炎症因子参与的慢性炎症性皮肤疾病,其中IL-1家族分子IL-36α与银屑病发生发展密切相关。在基因敲除小鼠研究中发现,当敲除IL-36α基因后,再用咪喹莫特制备小鼠银屑病样模型时,皮损和炎症都明显减轻。我们前期研究发现促炎因子Cyr61/CCN1能通过活化角质细胞、促进趋化因子产生而加剧银屑病发生,但其是否也参与IL-36α表达与调控则未见报道。本研究采用人永生化角质形成细胞(human immortalized keratinocytes cell line,HaCaT cell)在体外研究Cyr61对IL-36α表达的调控作用。结果发现Cyr61能显著上调HaCaT细胞表达IL-36α,而且呈剂量依赖性。进一步通过siRNA干扰技术下调HaCaT细胞中Cyr61的内源性表达,发现当Cyr61表达受抑制后,IL-36α表达也被有效抑制,表明Cyr61能够介导角质细胞表达IL-36α。已有报道表明TNF-α、IL-17和IL-22能够上调角质细胞表达IL-36α,因此我们还采用TNF-α、IL-17和IL-22特异性siRNA干扰这些炎症因子的内源性表达,观察Cyr61对IL-36α的作用。结果表明这些因子被干扰后并不影响Cyr61对IL-36α表达的影响,说明Cyr61能直接促进IL-36α表达。本研究的结果提示Cyr61/CCN1还可能通过上调IL-1家族分子IL-36α而参与银屑病发生。Psoriasis is a common chronic inflammatory skin disease which involves all kinds of inflammatory factors, and IL-36α of the IL-1 family is closely related to the development of psoriasis. IL-36α gene was knocked out in mice, and the psoriasis mice model was established by using imiquimod. The results showed that skin lesions and inflammation were reduced signifi cantly. Our previous study found pro-inflammatory factor Cyr61/CCN1 can aggravate psoriasis by promoting chemokines and activating keratinocytes, but the effect of Cyr61/CCN1 on the expression and regulation of IL-36α has not been reported. Using human keratinocytes cell line（HaCaT cells）, the present study explored the role of Cyr61 on the expression of IL-36α in vitro. The results showed that Cyr61 could significantly enhance the expression of IL-36α in HaCaT cells in a dose dependent manner. Furthermore, we found that after down-regulating the expression of Cyr61 in HaCaT cells by interference with siRNA, the expression of IL-36α was effectively suppressed, suggesting that Cyr61 enhanced the expression of IL-36α in HaCaT cells. As it has been reported that TNF-α, IL 17 and IL-22 could also increase the expression of IL-36α in HaCaT ceils, so we silenced TNF-α, IL-17 and IL-22 respectively with specific siRNAs and tested the effect of Cyr61 on the IL-36α expression. The results showed that these inflammatory factors did not influence the effect of Cyr61 on IL-36α expression, which suggests Cyr61 could directly promote the expression of IL-36α. Thus, our study demonstrates that Cyr61/CCN1 may play a role in the pathogenesis of psoriasis by up-regulating IL-36α expression in kerotinocytes.

关 键 词：银屑病 Cyr61/CCN1 IL-36α HACAT细胞 

分 类 号：R392[医药卫生—免疫学]