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

被引:32
|
作者
Wang, Wenhan [1 ]
Li, Zhong [2 ]
Meng, Qingjuan [3 ]
Zhang, Pei [1 ]
Yan, Pengcheng [1 ]
Zhang, Zhenbiao [1 ]
Zhang, Hao [1 ]
Pan, Jingrui [1 ]
Zhai, Yujia [1 ]
Liu, Yaoge [1 ]
Wang, Xiaokai [1 ]
Li, Weiwei [4 ]
Zhao, Yunpeng [5 ]
机构
[1] Shandong Univ, Sch Med, Jinan 250012, Shandong, Peoples R China
[2] Taishan Med Univ, Dept Orthopaed, Liaocheng Clin Acad, Liaocheng 252000, Shandong, Peoples R China
[3] Third Peoples Hosp Jinan, Jinan 250101, Shandong, Peoples R China
[4] Shandong Univ, Qilu Hosp, Dept Pathol, Jinan 250012, Shandong, Peoples R China
[5] Shandong Univ, Qilu Hosp, Dept Orthopaed, 107 Wenhuaxi Rd, Jinan 250012, Shandong, Peoples R China
基金
中国国家自然科学基金;
关键词
verapamil; TNF-alpha; NF-kB signaling; collagen-induced arthritis; COLLAGEN-INDUCED ARTHRITIS; TUMOR-NECROSIS-FACTOR; ACTIVE RHEUMATOID-ARTHRITIS; CYTOKINE PRODUCTION; MONONUCLEAR-CELLS; GENE-EXPRESSION; IN-VITRO; METHOTREXATE; PROGRANULIN; BLOCKERS;
D O I
10.1007/s10753-016-0396-1
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
It is well established that the tumor necrosis factor-alpha (TNF-alpha) 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-alpha-mediated inflammation reaction and the underlying mechanisms, bone marrow-derived macrophages (BMDM) cells were cultured with stimulation of TNF-alpha, 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-alpha-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-alpha-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.
引用
收藏
页码:1624 / 1634
页数:11
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