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Inflammation
Published in: Inflammation 5/2016

01-10-2016 | ORIGINAL ARTICLE

Chronic Calcium Channel Inhibitor Verapamil Antagonizes TNF-α-Mediated Inflammatory Reaction and Protects Against Inflammatory Arthritis in Mice

Authors: Wenhan Wang, Zhong Li, Qingjuan Meng, Pei Zhang, Pengcheng Yan, Zhenbiao Zhang, Hao Zhang, Jingrui Pan, Yujia Zhai, Yaoge Liu, Xiaokai Wang, Weiwei Li, Yunpeng Zhao

Published in: Inflammation | Issue 5/2016

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Abstract

It is well established that the tumor necrosis factor-α (TNF-α) plays a dominant role in rheumatoid arthritis (RA). Calcium channel is recently reported to be closely associated with various inflammatory diseases. However, whether chronic calcium channel blocker verapamil plays a role in RA still remains unknown. To investigate the role of verapamil in antagonizing TNF-α-mediated inflammation reaction and the underlying mechanisms, bone marrow-derived macrophages (BMDM) cells were cultured with stimulation of TNF-α, in the presence or absence of verapamil. Inflammation-associated cytokines, including IL-1, IL-6, inducible nitric oxide synthase 2 (NOS-2), and cyclooxygenase-2 (COX-2), were assessed, and verapamil suppressed TNF-α-induced expression of inflammatory cytokines. Furthermore, collagen-induced arthritis (CIA) mice models were established, and arthritis progression was evaluated by clinical and histological signs of arthritis. Treatment of verapamil attenuated inflammation as well as joint destruction in arthritis models. In addition, activity of NF-kB signaling pathway was determined both in vitro and in mice arthritis models, and verapamil inhibited TNF-α-induced activation of NF-kB signaling both in vitro and in mice models. Collectively, chronic calcium channel blocker verapamil may shed light on treatment of inflammatory arthritis and provide a potential therapeutic instrument for RA in the future.
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Metadata
Title
Chronic Calcium Channel Inhibitor Verapamil Antagonizes TNF-α-Mediated Inflammatory Reaction and Protects Against Inflammatory Arthritis in Mice
Authors
Wenhan Wang
Zhong Li
Qingjuan Meng
Pei Zhang
Pengcheng Yan
Zhenbiao Zhang
Hao Zhang
Jingrui Pan
Yujia Zhai
Yaoge Liu
Xiaokai Wang
Weiwei Li
Yunpeng Zhao
Publication date
01-10-2016
Publisher
Springer US
Published in
Inflammation / Issue 5/2016
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-016-0396-1

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