T Helper 1 and T Helper 2 Cytokines Differentially Modulate Expression of Filaggrin and its Processing Proteases in Human Keratinocytes.
T Helper 1 and T Helper 2 Cytokines Differentially Modulate Expression of Filaggrin and its Processing Proteases in Human Keratinocytes.
复制标题
T 辅助细胞 1 和 T 辅助细胞 2 细胞因子差异调节人角质形成细胞中丝聚蛋白及其加工蛋白酶的表达
DOI：
10.4103/0366-6999.174489
复制
发表时间：
2016-02-05
影响因子：
6.1
通讯作者：
Gao XH
中科院分区：
文献类型：
--
作者：
Di ZH;Ma L;Qi RQ;Sun XD;Huo W;Zhang L;Lyu YN;Hong YX;Chen HD;Gao XH
背景：特应性皮炎(AD)以皮肤屏障缺陷和Th1/Th2细胞因子表达失衡为特征。丝状蛋白(flaggrin，Flg)是维持皮肤屏障功能的关键蛋白。最近的研究表明，Th1/Th2细胞因子影响角质形成细胞中Flg的表达。然而，Th1/Th2细胞因子在Flg处理过程中的作用并没有实质性的文献记载。我们的目的是研究Th1/Th2细胞因子对Flg加工的影响。方法：在低钙和高钙条件下培养HaCaT细胞和正常人角质形成细胞，分别用白细胞介素4、13和干扰素刺激。用实时定量聚合酶链式反应和Western blotting检测Flg及其主要加工酶和关键蛋白抑制因子淋巴上皮Kazal型相关抑制物(Lekti)的表达。免疫组织化学方法检测其在急、慢性AD皮损中的表达。结果：IL-4/13显著降低，而干扰素-γ显著上调Flg的表达。IL-4/13显著增加，而干扰素-1显著降低激肽释放酶5、7、丝氨酸酶和通道激活丝氨酸蛋白酶1的表达。相反，IL-4/13显著降低，而干扰素-1和干扰素-1增加lekti和caspase-14的表达。在AD皮损中也观察到了类似的趋势。结论：我们的结果提示Th1/Th2细胞因子对主要的Flg加工酶的表达有不同的调节作用。Th1和Th2极化免疫反应之间的失衡似乎通过Flg处理酶网络延伸到Flg动态平衡。
Background:Atopic dermatitis (AD) is characterized by defective skin barrier and imbalance in T helper 1/T helper 2 (Th1/Th2) cytokine expression. Filaggrin (FLG) is the key protein to maintaining skin barrier function. Recent studies indicated that Th1/Th2 cytokines influence FLG expression in keratinocytes. However, the role of Th1/Th2 cytokines on FLG processing is not substantially documented. Our aim was to investigate the impact of Th1/Th2 cytokines on FLG processing. Methods:HaCaT cells and normal human keratinocytes were cultured in low and high calcium media and stimulated by either interleukin (IL)-4, 13 or interferon-&ggr; (IFN-&ggr;). FLG, its major processing proteases and key protease inhibitor lymphoepithelial Kazal-type-related inhibitor (LEKTI) were measured by both real-time quantitative polymerase chain reaction and Western blotting. Their expression was also evaluated in acute and chronic AD lesions by immunohistochemistry. Results:IL-4/13 significantly reduced, while IFN-&ggr; significantly up-regulated FLG expression. IL-4/13 significantly increased, whereas IFN-&ggr; significantly decreased the expression of kallikreins 5 and 7, matriptase and channel-activating serine protease 1. On the contrary, IL-4/13 significantly decreased, while IFN-&ggr; increased the expression of LEKTI and caspase-14. Similar trends were observed in AD lesions. Conclusions:Our results suggested that Th1/Th2 cytokines differentially regulated the expression of major FLG processing enzymes. The imbalance between Th1 and Th2 polarized immune response seems to extend to FLG homeostasis, through the network of FLG processing enzymes.