Effect Of Interleukin-34 On Secretion Of Angiogenesis Cytokines By Peripheral Blood Mononuclear Cells Of RA

Objective: Interleukin(IL)-34 is a new pro-inflammatory cytokine.Previous studies showed that IL-34 plays a key role in the inflammatory and osteoporosis of rheumatoid arthritis(RA).However,whether IL-34 takes part in the angiogenesis of RA is still unknown.Vascular endothelial growth factor(VEGF)and hypoxia-inducible factor-1?(HIF-1?)play key roles in the angiogenesis of RA.In this study,we detect the effect of IL-34 on the secretion of angiogenesis-related factors VEGF and HIF-1? by peripheral blood mononuclear cells(PBMC)of patients with RA.Methods: Twenty-two patients with RA and eight healthy subjects were enrolled in this study.PBMC were isolated and purified from peripheral blood by density gradient centrifugation.The PBMC were stimulated by anti-CD3/CD28 antibody and different concentrations of recombinant human(rh)IL-34(0,10,20,50,100ng/m L).Cell-free supernatants were collected after 72 hours incubation,and the levels of VEGF and HIF-1? were determined by enzyme-linked immunosorbent assay(ELISA).Results: IL-34 promotes the secretion of VEGF and HIF-1? by PBMC of patients with RA dose-dependently.In contrast,IL-34 has no effect on the secretion of VEGF and HIF-1? by PBMC of healthy controls.10,20,50 and 100ng/m L rh IL-34 elevated the secretion of VEGF by PBMC of RA patients compared with 0ng/m L rh IL-34(79.20 ±16.31 pg/m L)(p<0.01).The level of VEGF under the stimulation of 20ng/m L rh IL-34(99.28 ± 19.51 pg/m L)was higher than 10ng/m L group(86.75 ± 17.19 pg/m L)(p<0.01).Furthermore,50ng/m L group(108.9 ± 20.94 pg/m L)was significantly higher than20ng/m L(p<0.05).However,there was no significant difference between the 100ng/m L group(107.3 ± 19.03 pg/m L)and the 50ng/m L group.The level of HIF-1? under the stimulation of 10 and 20ng/m L rh IL-34(16.94 ± 0.39 pg/m L,16.84 ± 0.37 pg/m L)were not significantly higher than 0ng/m L group(17.38 ± 0.66 pg/m L).50 and 100ng/m L groups(19.91 ± 0.83 pg/m L,24.61 ± 1.36 pg/m L)were significantly higher than 0ng/m L(p<0.05,p<0.01,respectively).Furthermore,100ng/m L group higher than 50ng/m L(p<0.01).Conclusion: IL-34 can promote the secretion of VEGF and HIF-1? by PBMC of RA patients.It suggested that IL-34 may indirectly promote angiogenesis by promoting the secretion of VEGF and HIF-1? and play a role in the pathogenesis of RA.