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Abstract: Objective To investigate the effect of GSK484 on neutrophil extracellular traps(NETs) formation and inflammatory response in ankylosing spondylitis (AS) and its related mechanisms. Methods The levels of PAD4, H3cit, IL-1β, IL-6, and the formation of NETs were assessedin peripheral blood from AS patients and healthy subjects. Thirty Balb/ c mice were divided into 3 groups: control, model, and GSK484 treatment groups. The model and GSK484 treatment groups were subjected to an AS model induction, followed by oral administration of 4 mg / kg GSK484 for a week in the treatment group, while the other groups received an equivalent volume of saline. Ankle joint damage scores, NETs levels, and the levels of PAD4, H3cit, IL-6, and IFN-γ were compared among the groups aftertreatment. Results Compared to healthy subjects, AS patients showed elevated levels of PAD4, H3cit,IL-1β, IL-6, and increased formation of NETs. The GSK484 treatment group exhibited reduced ankle joint damage scores, NETs formation, and levels of PAD4, H3cit, IL-1β, IL-6 compared to the modelgroup. Conclusion GSK484 inhibits the formation of NETs, offering a new therapeutic strategy for alleviating the inflammatory response in AS.

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