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IL-17A induction of ADAMTS-5 in differentiated THP-1 cells is modulated by the ERK signaling pathway
European Cytokine Network ( IF 2.2 ) Pub Date : 2020-10-02 , DOI: 10.1684/ecn.2020.0446
Esther Mun Huieh Thou 1 , Quok Cheong Choo 2 , Choy Hoong Chew 1
Affiliation  

Atherosclerosis is initiated when lipoproteins are trapped by proteoglycans in the arterial intima. Macrophages play a vital role in this disease, especially in the formation of foam cells and the regulation of proinflammatory responses. They also participate in plaque stabilization through the secretion of matrix metalloproteinases. Studies have reported the role of ADAMTS proteases in osteoarthritis and atherosclerotic lesions. In the present study, we have studied the effect of interleukin-17A (IL-17A) on the expression of ADAMTS-5 in the macrophage cell line THP-1. The results show that the mRNA and protein expression levels of ADAMTS-5 were significantly upregulated when differentiated THP-1 cells were treated with 100 ng/mL of IL-17A for 24 h with maximum ADAMTS-5 mRNA expression levels obtained at 8 h of stimulation. Subsequent inhibition studies showed that IL-17A upregulation of ADAMTS-5 was mediated through ERK and JNK pathways in THP-1 cells. Phosphorylation studies revealed that the expression of ADAMTS-5 transcripts was upregulated by IL-17A through the activation of p-c-Raf (S338), p-MEK1/2 (Ser217/221), p-p44/42 MAPK (Thr202/Tyr204), and p-Elk1 (Ser383). ERK1/2 siRNA transfection further confirmed that the ERK pathway is involved in the expression of ADAMTS-5 in IL-17A-stimulated THP-1 cells.



中文翻译:

IL-17A 在分化的 THP-1 细胞中诱导 ADAMTS-5 由 ERK 信号通路调节

当脂蛋白被动脉内膜中的蛋白聚糖捕获时,动脉粥样硬化就开始了。巨噬细胞在这种疾病中发挥着至关重要的作用,特别是在泡沫细胞的形成和促炎反应的调节中。它们还通过分泌基质金属蛋白酶参与斑块稳定。研究报道了 ADAMTS 蛋白酶在骨关节炎和动脉粥样硬化病变中的作用。在本研究中,我们研究了白介素17A (IL-17A)对巨噬细胞系THP-1中ADAMTS-5表达的影响。结果表明,当分化的THP-1细胞用100 ng/mL的IL-17A处理24小时时,ADAMTS-5的mRNA和蛋白表达水平显着上调,并且在8小时时获得最大ADAMTS-5 mRNA表达水平。刺激。随后的抑制研究表明,IL-17A 对 ADAMTS-5 的上调是通过 THP-1 细胞中的 ERK 和 JNK 途径介导的。磷酸化研究表明,IL-17A 通过激活 pc-Raf (S338)、p-MEK1/2 (Ser217/221)、p-p44/42 MAPK (Thr202/Tyr204) 上调 ADAMTS-5 转录本的表达和 p-Elk1 (Ser383)。 ERK1/2 siRNA转染进一步证实ERK通路参与IL-17A刺激的THP-1细胞中ADAMTS-5的表达。

更新日期:2020-10-02
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