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Chronic Calcium Channel Inhibitor Verapamil Antagonizes TNF-α-Mediated Inflammatory Reaction and Protects Against Inflammatory Arthritis in Mice
- Source :
- Inflammation. 39:1624-1634
- Publication Year :
- 2016
- Publisher :
- Springer Science and Business Media LLC, 2016.
-
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.
- Subjects :
- 0301 basic medicine
medicine.drug_class
Inflammatory arthritis
Immunology
Arthritis
Inflammation
Calcium channel blocker
Pharmacology
Proinflammatory cytokine
Mice
03 medical and health sciences
Animals
Immunology and Allergy
Medicine
Tumor Necrosis Factor-alpha
business.industry
Calcium channel
NF-kappa B
Calcium Channel Blockers
medicine.disease
Arthritis, Experimental
030104 developmental biology
Verapamil
Joints
Tumor necrosis factor alpha
Collagen
Inflammation Mediators
medicine.symptom
business
medicine.drug
Subjects
Details
- ISSN :
- 15732576 and 03603997
- Volume :
- 39
- Database :
- OpenAIRE
- Journal :
- Inflammation
- Accession number :
- edsair.doi.dedup.....2378e2a2e1c03329aa343f8bfbca12f3