Abstract
BackgroundNeutrophil extracellular trap (NET) formation has been described to be closely involved in the pathogenesis of systemic lupus erythematosus (SLE). In this study, we aimed to investigate the effect of polydatin (PD) on NET formation and its effects on disease activity in lupus-prone mouse models.MethodsIn vitro, neutrophils from SLE patients and healthy people stimulated with phorbol 12-myristate 13-acetate (PMA) or phosphate-buffered saline (PBS) were treated with PD, and reactive oxygen species (ROS) production and NET formation examined. In vivo, pristane-induced lupus (PIL) mice were treated with vehicle, PD, mycophenolate mofetil (MMF) or cyclophosphamide (CYC) while MRL/lpr mice were treated with vehicle or PD. Proteinuria, serum autoantibodies, ROS production, NET formation and kidney histopathology were tested.ResultsConsistent with previous findings, blood neutrophils from SLE patients showed increased spontaneous NET formation. Both in vivo and in vitro, PD treatment significantly inhibited ROS production and NET release by neutrophils. In MRL/lpr mouse model, PD administration reduced the proteinuria, circulating autoantibody levels, and deposition of NETs and immune complex in the kidneys. In addition, PD treatment ameliorated lupus-like features in PIL mice as MMF or CYC did.ConclusionsPD treatment inhibited ROS-mediated NET formation and ameliorated lupus manifestations in both PIL mice and MRL/lpr mice. These results highlight the involvement of NETosis in SLE pathogenesis and reveal that PD might be a potential therapeutic agent for SLE or other autoimmune diseases.
Highlights
Systemic lupus erythematosus (SLE) is a chronic progressive autoimmune disorder manifested by autoantibody overproduction and multi-organ involvement [1]
systemic lupus erythematosus (SLE) patients showed enhanced spontaneous Neutrophil extracellular trap (NET) formation Previous studies have indicated that neutrophils from SLE patients exhibit high potential for spontaneous NET formation
To test spontaneous NET formation, neutrophils were isolated from SLE patients and healthy controls (HCs), and cultured in RPMI-1640 for 4 h
Summary
Systemic lupus erythematosus (SLE) is a chronic progressive autoimmune disorder manifested by autoantibody overproduction and multi-organ involvement [1]. It is prominently prevalent in African, Asian, Hispanic and American patients [2] and mostly occurs in young women [3]. Neutrophils, the most abundant sensory and effector cells in the innate immune system, have attracted more attention in recent years [7]. Neutrophils from SLE patients have been shown to exhibit an increased propensity for NET formation [7, 10]. Neutrophil extracellular trap (NET) formation has been described to be closely involved in the pathogenesis of systemic lupus erythematosus (SLE). We aimed to investigate the effect of polydatin (PD) on NET formation and its effects on disease activity in lupus-prone mouse models
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