Open Access

ORIGINAL ARTICLE

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

Esther Mun Huieh Thou¹, Quok Cheong Choo², Choy Hoong Chew¹

1 Department of Allied Health Sciences, Universiti Tunku Abdul Rahman, Faculty of Science, 31900 Kampar, Perak
2 Department of Biological Science, Universiti Tunku Abdul Rahman, Faculty of Science, 31900 Kampar, Perak

* Corresponding Author: Choy Hoong Chew,

European Cytokine Network 2020, 31(2), 59-67. https://doi.org/10.1684/ecn.2020.0446

Accepted 28 February 2020;

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 pro-inflammatory 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.

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