OBJECTIVE This study aimed to evaluate the protective effect of igalan, a sesquiterpene lactone isolated from Inula helenium (L.), on inhibiting inflammation, regulating the epidermal differentiation gene expression, and reactive oxygen species scavenging in atopic dermatitis (AD)-like inflammatory keratinocytes. METHODS HaCaT human keratinocytes were treated with igalan at indicated concentrations before being activated by a combination of TNF-α and IFN-γ or IL-4 representative for T-helper 1 and T-helper 2 cell cytokines, which are associated with AD pathogenesis. RESULTS By inhibiting the NF-κB pathway as well as the STAT activation, igalan could downregulate several marker inflammatory genes in AD, such as TARC/CCL17, MDC/CCL22, and RANTES/CCL5. In contrast, igalan, acting as JAK inhibitor, could promote the mRNA expression levels of the genes FLG, LOR, KRT10, and DSC1, which encode for essential proteins responsible for keratinocyte differentiation, by inhibiting STAT3 signaling. Furthermore, igalan exerts its antioxidant effect through activating the Nrf2 pathway, triggering the expression of some enzymes that contribute to preventing intracellular ROS generation during inflammation. CONCLUSION These findings indicate that igalan, via suppressing JAK/STAT3 signaling, could impair the production of pro-inflammatory chemokines and enhance expression levels of several genes involved in keratinocyte differentiation in AD-like stimulated keratinocytes.

中文翻译：

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来自Inula helenium（L.）的Igalan通过JAK / STAT3信号传导抑制刺激的HaCaT角质形成细胞中的特应性皮炎样反应。

目的本研究旨在评估从菊粉（Inula helenium，L.）中分离出的倍半萜内酯igalan抑制炎症，调节表皮分化基因表达以及清除类似特应性皮炎（AD）的炎症性角质形成细胞中的活性氧的保护作用。 。方法HagaT人角质形成细胞用指定浓度的伊兰胶处理，然后被代表T辅助1和T辅助2细胞因子的TNF-α和IFN-γ或IL-4联合激活，这与AD发病机理有关。结果通过抑制NF-κB途径和STAT激活，igalan可以下调AD中的几种标志性炎症基因，如TARC / CCL17，MDC / CCL22和RANTES / CCL5。相反，作为JAK抑制剂的igalan 通过抑制STAT3信号转导，可以促进FLG，LOR，KRT10和DSC1基因的mRNA表达水平，这些基因编码负责角质形成细胞分化的必需蛋白。此外，igalan通过激活Nrf2途径发挥其抗氧化作用，触发某些酶的表达，这些酶有助于防止炎症过程中细胞内ROS的产生。结论这些发现表明，通过抑制JAK / STAT3信号传导，igalan可能会损害促炎性趋化因子的产生，并增强AD样角质形成细胞中参与角质形成细胞分化的几个基因的表达水平。igalan通过激活Nrf2途径发挥抗氧化作用，触发某些酶的表达，这些酶有助于防止炎症过程中细胞内ROS的产生。结论这些发现表明，通过抑制JAK / STAT3信号传导，igalan可能会损害促炎性趋化因子的产生，并增强AD样角质形成细胞中参与角质形成细胞分化的几个基因的表达水平。igalan通过激活Nrf2途径发挥其抗氧化作用，触发某些酶的表达，这些酶有助于防止炎症过程中细胞内ROS的产生。结论这些发现表明，通过抑制JAK / STAT3信号传导，igalan可能会损害促炎性趋化因子的产生，并增强AD样角质形成细胞中参与角质形成细胞分化的几个基因的表达水平。