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

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European Cytokine Network

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.

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Authors and Affiliations

  1. Department of Allied Health Sciences, Faculty of Science, Universiti Tunku Abdul Rahman, Jalan Universiti Bandar Barat, 31900, Kampar, Perak, Malaysia

    Esther Mun Huieh Thou & Choy Hoong Chew

  2. Department of Biological Science, Faculty of Science, Universiti Tunku Abdul Rahman, 31900, Kampar, Perak, Malaysia

    Quok Cheong Choo

Authors
  1. Esther Mun Huieh Thou
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  2. Quok Cheong Choo
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  3. Choy Hoong Chew
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Correspondence to Choy Hoong Chew.

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No competing financial interests exist.

Funding

This work was supported by the Universiti Tunku Abdul Rahman Research Fund (UTARRF) (6200/CD7); and the Malaysia Toray Science Foundation (MTSF) (4417/ E01).

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Thou, E.M.H., Choo, Q.C. & Chew, C.H. IL-17A induction of ADAMTS-5 in differentiated THP-1 cells is modulated by the ERK signaling pathway. Eur Cytokine Netw 31, 59–67 (2020). https://doi.org/10.1684/ecn.2020.0446

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