The Role Of IL-8 Expression Promoted By Transcription Factor YY1 In The Pathogenesis Of Rheumatoid Arthritis

ObjectiveThis study aims to explore the correlation between IL-8 and YY1 in the pathogenesis of rheumatoid arthritis and its possible signaling pathway involved.Methods1.YY1 and IL-8 expression in RA patients were analyzed by real-time PCR.2.Ingenuity pathway analysis(IPA)was used to analyzed signaling pathway involved in YY1-induced IL-8 production.3.The expression of YY1 and proteins involved in pathway were detected by western blot and ELISA.4.Migration of neutrophils was performed by transwell assay with co-culture of PBMC and neutrophils.5.CIA mouse model was injected with LV-YY1-shRNA and LV-NC through the tail vein and its inflammation level,neutrophil infiltration and cytokine expression were determined..Results1.High expression of IL-8 was positively associated with YY1 expression in RA.IL-8 expression was reduced by blocking YY1 with YY1-shRNA lentivirus.2.IL-8 production was activated by YY1 via PI3K/Akt/mTOR signaling pathway.3.The migration of neutrophils was inhibited by YY1 RNA interference.4.Arthritis mice were treated with YY1-shRNA lentivirus and showed reduction of IL-8 levels and attenuation of inflammation and neutrophils infiltration in vivo.ConclusionsIL-8 production was induced by YY1 via PI3K-Akt-mTOR signaling pathway in patients with rheumatoid arthritis which may promote the neutrophils infiltration and disease development.This finding indicates that YY1 could be served as a candidate target for RA therapy.