Regulation of Arthritis Severity by the Acid Sphingomyelinase.
Cell Physiol Biochem
; 43(4): 1460-1471, 2017.
Article
in En
| MEDLINE
| ID: mdl-29035882
ABSTRACT
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Arthritis, Experimental
/
Sphingomyelin Phosphodiesterase
/
Joints
Limits:
Animals
Language:
En
Journal:
Cell Physiol Biochem
Journal subject:
BIOQUIMICA
/
FARMACOLOGIA
Year:
2017
Document type:
Article
Affiliation country:
Germany