肿瘤坏死因子α
银屑病
调节器
白细胞介素
细胞因子
白细胞介素17
p38丝裂原活化蛋白激酶
白细胞介素20
癌症研究
角质形成细胞
白细胞介素19
免疫学
白细胞介素6
信号转导
白细胞介素8
细胞生物学
生物
白细胞介素10
白细胞介素23
促炎细胞因子
白细胞介素18
哈卡特
MAPK/ERK通路
基因
白细胞介素5
遗传学
作者
Sofie Kaas Ovesen,Klaus Schulze-Osthoff,Lars Iversen,Claus Johansen
标识
DOI:10.2340/00015555-3749
摘要
The interleukin (IL)-36 cytokine family plays an essential role in inflammatory processes in the skin and is implicated in the pathogenesis of psoriasis. This study explored the role of IL-36 in psoriasis and investigated the molecular mechanism involved in tumour necrosis factor-α (TNFα)/IL-17A-mediated IL-36 induction. In human keratinocytes IL-36 expression was strongly upregulated by combined TNFα and IL-17A stimulation. Moreover, IκBζ, encoded by NFKBIZ, was identified as a key regulator required for TNFα/IL-17A-induced IL-36γ expression. TNFα/IL-17A-induced IL-36γ expression also involved the nuclear factor κB (NF-κB), p38 mitogen-activated protein kinase and ERK1/2 signalling pathways. Furthermore, a specific NF-κB DNA-binding site in the promoter region of IL36G responsible for the TNFα/IL-17A-induced IL36G gene expression was identified. Finally, in a cohort of patients with psoriasis receiving anti-IL-17A treatment, a positive correlation was found between the expression of NFKBIZ and IL36G. In conclusion, these data reveal a novel crucial regulatory mechanism by which TNFα and IL-17A regulate IL-36γ expression.
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