Universität zu Köln

Beckmann, Nadine, Becker, Katrin Anne, Walter, Silke, Becker, Jan U., Kramer, Melanie, Hessler, Gabriele, Weber, Stefanie, Goethert, Joachim R., Fassbender, Klaus ORCID: 0000-0003-3596-868X, Gulbins, Erich and Carpinteiro, Alexander (2017). Regulation of Arthritis Severity by the Acid Sphingomyelinase. Cell. Physiol. Biochem., 43 (4). S. 1460 - 1472. BASEL: KARGER. ISSN 1421-9778

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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. (C) 2017 The Author(s) Published by S. Karger AG, Basel

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Beckmann, Nadine UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Katrin Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Walter, Silke UNSPECIFIED UNSPECIFIED UNSPECIFIED Becker, Jan U. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kramer, Melanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Hessler, Gabriele UNSPECIFIED UNSPECIFIED UNSPECIFIED Weber, Stefanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Goethert, Joachim R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fassbender, Klaus UNSPECIFIED orcid.org/0000-0003-3596-868X UNSPECIFIED Gulbins, Erich UNSPECIFIED UNSPECIFIED UNSPECIFIED Carpinteiro, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-244900
DOI:	10.1159/000481968
Journal or Publication Title:	Cell. Physiol. Biochem.
Volume:	43
Number:	4
Page Range:	S. 1460 - 1472
Date:	2017
Publisher:	KARGER
Place of Publication:	BASEL
ISSN:	1421-9778
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MEMORY T-CELLS; N-TERMINAL KINASE; RHEUMATOID-ARTHRITIS; SYNOVIAL-FLUID; FUNCTIONAL INHIBITORS; ENDOTHELIAL-CELLS; P-SELECTIN; INFLAMMATION; THERAPY; DISEASE Multiple languages Cell Biology; Physiology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/24490