title: Chronic Calcium Channel Inhibitor Verapamil Antagonizes TNF-α-Mediated Inflammatory Reaction and Protects Against Inflammatory Arthritis in Mice.
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.
authors.affiliation: School of Medicine, Shandong University, Jinan, Shandong, 250012, People's Republic of China.
authors.forename: Wenhan
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, Liaocheng Clinical Academy, Taishan Medical University, Liaocheng, Shandong, 252000, People's Republic of China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Li
authors.affiliation: The Third People's Hospital of Jinan, Jinan, Shandong, 250101, People's Republic of China.
authors.forename: Qingjuan
authors.initials: Q
authors.lastname: Meng
authors.affiliation: School of Medicine, Shandong University, Jinan, Shandong, 250012, People's Republic of China.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: School of Medicine, Shandong University, Jinan, Shandong, 250012, People's Republic of China.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Yan
authors.affiliation: School of Medicine, Shandong University, Jinan, Shandong, 250012, People's Republic of China.
authors.forename: Zhenbiao
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Medicine, Shandong University, Jinan, Shandong, 250012, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Medicine, Shandong University, Jinan, Shandong, 250012, People's Republic of China.
authors.forename: Jingrui
authors.initials: J
authors.lastname: Pan
authors.affiliation: School of Medicine, Shandong University, Jinan, Shandong, 250012, People's Republic of China.
authors.forename: Yujia
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: School of Medicine, Shandong University, Jinan, Shandong, 250012, People's Republic of China.
authors.forename: Yaoge
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Medicine, Shandong University, Jinan, Shandong, 250012, People's Republic of China.
authors.forename: Xiaokai
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pathology, Qilu Hospital, Shandong University, Jinan, Shandong, 250012, People's Republic of China. liweiweizhao@163.com.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan, Shandong, 250012, People's Republic of China. yishengwwh@163.com.
authors.forename: Yunpeng
authors.identifier: http://orcid.org/0000-0002-5483-3978
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D003094:Collagen; D007249:Inflammation / Q000188:drug therapy; D018836:Inflammation Mediators / Q000502:physiology; D007596:Joints / Q000187:drug effects / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects* / Q000502:physiology; D014700:Verapamil / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D002121:Calcium Channel Blockers; D018836:Inflammation Mediators; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen; D014700:Verapamil
keywords: NF-kB signaling; TNF-α; collagen-induced arthritis; verapamil