Arthritis & rheumatology (Hoboken, N.J.) · 2015
Pantethine Prevents Murine Systemic Sclerosis Through the Inhibition of Microparticle Shedding.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Kavian Niloufar, Marut Wioleta, Servettaz Amélie, Nicco Carole, Chéreau Christiane, Lemaréchal Hervé, Guilpain Philippe, Chimini Giovanna, Galland Franck, Weill Bernard, Naquet Philippe, Batteux Frédéric
Аннотация
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.
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.
Предметные рубрики MeSH
ATP Binding Cassette Transporter 1Administration, OralAnimalsBleomycinCell-Derived MicroparticlesCells, CulturedDisease Models, AnimalEndothelial CellsFemaleFibroblastsHomeostasisHypochlorous AcidIn Vitro TechniquesInjections, IntradermalMiceMice, Inbred BALB CMice, KnockoutOxidative StressPantetheineScleroderma, SystemicTreatment Outcome