Bertelsen Trine, Iversen Lars, Johansen Claus
Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
Ann Dermatol. 2021 Apr;33(2):122-130. doi: 10.5021/ad.2021.33.2.122. Epub 2021 Mar 8.
Interleukin (IL)-19 and IL-20 are important members of the IL-10 cytokine family, which are known to play a role in inflammatory processes. Both anti-IL-19 and -IL-20 targeting drugs have been suggested in the treatment of inflammatory diseases such as psoriasis and rheumatoid arthritis. Recently, we presented I-kappa-B-zeta (IκBζ) as a key player in psoriasis by identifying IκBζ as a regulator of IL-17/tumor necrosis factor (TNF)α-inducible psoriasis-associated genes and proteins. Some of these genes were synergistically regulated by IL-17/TNFα.
The purpose of this study was to explore the role of IκBζ in the regulation of IL-17A/TNFα-mediated induction of IL-19 and IL-20 expression in human keratinocytes.
experiments with cultured primary humane keratinocytes were conducted and investigated by quantitative polymerase chain reaction (qPCR), Western blotting, ELISA and EMSA. For statistics, a one- or two- way repeated-measures analysis of variance (RM ANOVA) or the Friedman test (a nonparametric equivalent to the RM ANOVA) were conducted.
We demonstrated that IL-19 and IL-20 mRNA and protein expressions were synergistically induced by IL-17A and TNFα, whereas IL-17A and TNFα alone had only a minor effect on the IL-19 and IL-20 expression. Moreover, we demonstrated IκBζ to be a regulator of this synergistic induction of IL-19 and IL-20. Finally, the IL-17A/TNFα-induced synergistic induction of IL-19 and IL-20 expression was found to be mediated by a p38 MAPK-, NF-κB- and JNK1/2-dependent mechanism.
This study demonstrates that IκBζ plays a role in the IL-17A/TNFα-mediated synergistic induction of IL-19 and IL-20 in humane keratinocytes.
白细胞介素（IL）-19和IL-20是IL-10细胞因子家族的重要成员，已知它们在炎症过程中发挥作用。抗IL-19和抗IL-20靶向药物已被建议用于治疗银屑病和类风湿性关节炎等炎症性疾病。最近，我们通过将I-κB-ζ（IκBζ）鉴定为IL-17/肿瘤坏死因子（TNF）α诱导的银屑病相关基因和蛋白质的调节因子，提出IκBζ是银屑病的关键参与者。其中一些基因受到IL-17/TNFα的协同调节。
本研究的目的是探讨IκBζ在调节人角质形成细胞中IL-17A/TNFα介导的IL-19和IL-20表达诱导中的作用。
对培养的原代人角质形成细胞进行实验，并通过定量聚合酶链反应（qPCR）、蛋白质印迹法、酶联免疫吸附测定（ELISA）和电泳迁移率变动分析（EMSA）进行研究。统计学分析采用单向或双向重复测量方差分析（RM ANOVA）或Friedman检验（RM ANOVA的非参数等效方法）。
我们证明IL-17A和TNFα协同诱导IL-19和IL-20的mRNA和蛋白质表达，而单独的IL-17A和TNFα对IL-19和IL-20的表达只有轻微影响。此外，我们证明IκBζ是IL-19和IL-20这种协同诱导的调节因子。最后，发现IL-17A/TNFα诱导的IL-19和IL-20表达的协同诱导是由p38丝裂原活化蛋白激酶（MAPK）、核因子κB（NF-κB）和应激活化蛋白激酶1/2（JNK1/2）依赖性机制介导的。
本研究表明IκBζ在人角质形成细胞中IL-17A/TNFα介导的IL-19和IL-20协同诱导中发挥作用。
