Influence of adalimumab on interleukin 12/23 signalling pathways in human keratinocytes treated with lipopolysaccharide A.

Paulina Buda, Piotr Michalski, Oliwia Warmusz, Anna Michalska-Bańkowska, Tomasz Sirek, Piotr Ossowski, Paweł Bogdał, Damian Strojny, Anna Pisany-Syska, Beniamin Oskar Grabarek
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Abstract

Introduction: The interleukin-12/23 (IL-12/23) signalling pathway plays an important role in the pathogenesis of psoriasis. In addition, even molecularly targeted therapy has been reported to lose adequate response to treatment.

Aim: To determine the expression patterns of mRNAs and miRNAs related to IL-12/23 signalling pathways in the human keratinocyte culture exposed to liposaccharide A (LPS) and then adalimumab in comparison with untreated cells.

Material and methods: Human, adult, low-Calcium, high-Temperature keratinocyte (HaCaT) cultures were exposed to 1 µg/ml LPS for 8 h, and then adalimumab was added to the cultures at a concentration of 8 µg/ml and incubated for 2, 8, and 24 h. We used mRNA and miRNA microarray, quantitative reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay techniques.

Results: STAT1, STAT3, STAT5, IL-6, IL-6R, SOCS3, and JAK3 genes differentiated HaCaT cultures with the drug from controls regardless of the time the cells were exposed to the drug. The addition of adalimumab to a culture previously exposed to LPS resulted in silencing of SOCS3 and IL-6 expression compared to the control, while for the other transcripts they were found to be overexpressed compared to the control culture. The assessment indicated the strongest connections between JAK3 and hsa-miR-373-5p (target score 96); SOCS3, STAT5, and hsa-miR-1827 (target score 96).

Conclusions: Our study indicates that adalimumab has the strongest modulating effect on mRNA and miRNA expression of JAK/STAT and IL-6-dependent IL-12/23 pathways.

阿达木单抗对脂多糖A处理人角质形成细胞白细胞介素12/23信号通路的影响
白介素-12/23 (IL-12/23)信号通路在银屑病的发病过程中起重要作用。此外,据报道,即使是分子靶向治疗也会对治疗失去足够的反应。目的:比较暴露于脂多糖A (LPS)和阿达木单抗的人角质细胞培养物中与IL-12/23信号通路相关的mrna和mirna的表达模式。材料和方法:将人、成人、低钙、高温角质细胞(HaCaT)培养物暴露于1µg/ml LPS中8小时,然后以8µg/ml的浓度添加阿达木单抗,孵育2、8和24小时。我们使用mRNA和miRNA微阵列、定量逆转录聚合酶链反应和酶联免疫吸附测定技术。结果:STAT1、STAT3、STAT5、IL-6、IL-6R、SOCS3和JAK3基因与药物作用的HaCaT培养物不同于对照组,与细胞暴露于药物的时间无关。与对照组相比,将阿达木单抗添加到先前暴露于LPS的培养物中导致SOCS3和IL-6表达沉默,而其他转录本则被发现与对照培养物相比过表达。评估表明JAK3与hsa-miR-373-5p之间的联系最强(目标评分为96);SOCS3, STAT5和hsa-miR-1827(目标评分96)。结论:我们的研究表明,阿达木单抗对JAK/STAT和il -6依赖性IL-12/23通路的mRNA和miRNA表达具有最强的调节作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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