Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 43, Issue 4, Pages 1460-1471Publisher
KARGER
DOI: 10.1159/000481968
Keywords
Rheumatoid arthritis; Acid sphingomyelinase; Ceramide; Inflammation
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Funding
- DFG [GU 335-35/1]
- GRK [2098]
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Background/Aims: Rheumatoid arthritis is a chronic autoimmune disease hallmarked by inflammation in synovial joints. Treatment is hampered by the lack of a cure and current disease-modifying drugs are associated with potentially severe toxicities. Methods: We investigated arthritis severity by measuring joint swelling and pro-inflammatory cytokine production in a murine experimental model of inflammatory arthritis (antigen-induced arthritis). We analyzed acid sphingomyelinase knock-out mice and wild-type littermates, as well as mice treated with the pharmacological acid sphingomyelinase inhibitor amitriptyline. Results: Genetic ablation or pharmacological inhibition of acid sphingomyelinase reduced joint swelling and levels of pro-inflammatory cytokines in the arthritic joint. Conclusion: We identified acid sphingomyelinase as a novel druggable target in rheumatoid arthritis. Functional inhibitors of acid sphingomyelinase have been clinically used for decades, are well tolerated and suitable for long-term treatment. They would be immediately available for clinical development as a novel rheumatoid arthritis therapy. (C) 2017 The Author(s) Published by S. Karger AG, Basel
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