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Pantethine Prevents Murine Systemic Sclerosis Through the Inhibition of Microparticle Shedding
Author(s) -
Kavian Niloufar,
Marut Wioleta,
Servettaz Amélie,
Nicco Carole,
Chéreau Christiane,
Lemaréchal Hervé,
Guilpain Philippe,
Chimini Giovanna,
Galland Franck,
Weill Bernard,
Naquet Philippe,
Batteux Frédéric
Publication year - 2015
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.39121
Subject(s) - in vivo , oxidative stress , pharmacology , chemistry , ex vivo , in vitro , biology , biochemistry , microbiology and biotechnology
Objective Endothelial cell (EC) damage in systemic sclerosis (SSc) is reflected by the shedding of microparticles (MPs). The aim of this study was to show that inhibiting MP release using pantethine or by inactivating ATP‐binding cassette transporter A1 (ABCA1) ameliorates murine SSc. Methods First, the effects of pantethine on MP shedding and on basal oxidative and nitrosative stresses in ECs and fibroblasts were determined in vitro. The effects of pantethine were then tested in vivo. SSc was induced in BALB/c mice by daily intradermal injection of HOCl. Mice were simultaneously treated daily with pantethine by oral gavage. Results In vitro, pantethine inhibited MP shedding from tumor necrosis factor–stimulated ECs and abrogated MP‐induced oxidative and nitrosative stresses in ECs and fibroblasts. Ex vivo, pantethine also restored redox homeostasis in fibroblasts from mice with SSc. In vivo, mice with SSc displayed skin and lung fibrosis associated with increased levels of circulating MPs and markers of oxidative and endothelial stress, which were normalized by administration of pantethine or inactivation of ABCA1 . Conclusion Pantethine is a well‐tolerated molecule that represents a potential treatment of human SSc.