Inhibition of NET formation by polydatin protects against collagen-induced arthritis

Background: Rheumatoid arthritis (RA) is a systematic, inflammatory, autoimmune disease, associated with a high number of disabilities. Increasing evidence has demonstrated that neutrophil extracellular trap (NET) formation plays a significant role in the pathogenesis and progression of RA. In this study, we have aimed to investigate the effects of polydatin (PD) on NET formation and its effects on disease activity in a collagen-induced arthritis (CIA) mouse model. Methods: In the presence of PD or vehicle, neutrophils isolated from RA patients and mice were treated with phorbol 12-myristate 13-acetate (PMA) for 4 h, and NET formation investigated. For in vivo experiments, PD was administered intraperitoneally (45 mg/kg per day) to collagen-induced arthritis (CIA) mice. The incidence and severity of collagen-induced arthritis were assessed and NET deposition tested. Results: In vitro, PD significantly suppressed NET formation of neutrophils from RA patients. Consistently, decreased NETs were observed in PD treated bone marrow-derived neutrophils. In CIA mouse model, PD treatment delayed the onset of arthritis and attenuated arthritis severity. Compared with vehicle-treated CIA mice, the deposition of NETS in ankle joints was also reduced in PD-treated CIA mice. Conclusion: In this study, we found that PD treatment markedly inhibited NET formation and protected CIA mice from the development of arthritis. These findings suggest that inhibition of NET formation by PD may serve as a novel mechanism for the treatment of RA.