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IL-17A induction of ADAMTS-5 in differentiated THP-1 cells is modulated by the ERK signaling pathway

IL-17A induction of ADAMTS-5 in differentiated THP-1 cells is modulated by the ERK signaling pathway 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Cytokine Network Springer Journals

IL-17A induction of ADAMTS-5 in differentiated THP-1 cells is modulated by the ERK signaling pathway

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Publisher
Springer Journals
Copyright
Copyright © JLE/Springer 2020
eISSN
1952-4005
DOI
10.1684/ecn.2020.0446
Publisher site
See Article on Publisher Site

Abstract

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.

Journal

European Cytokine NetworkSpringer Journals

Published: Jun 2, 2020

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