Interleukin-17 induces angiogenesis invitro via CXCL8 and CCL2 in retinal pigment epithelium.

Abstract

Interleukin-17 (IL-17) is a major pro-inflammatory cytokine involved in choroidal endothelial cell (CEC) angiogenesis. Proteins expressed by the retinal pigment epithelium (RPE) may contribute to CEC angiogenesis. The ability of IL‑17 to promote proliferation, migration and capillary‑like structure formation in CECs was investigated by stimulating the RPE invitro. CECs were cultured in a conditioned medium (CM) with IL‑17 (IL‑17‑CM) or without IL‑17 (CM) obtained from the supernatant of an ARPE‑19 cell line. The pro‑angiogenic role of IL‑17‑CM on CECs was investigated with water‑soluble tetrazolium 1 analysis, wound healing and Matrigel matrix tube formation assays. The expression level of vascular endothelial growth factor was detected by enzyme‑linked immunosorbent assay in RPE cells treated with or without IL‑17. Ras‑related C3botulinum toxin substrate 1 (Rac1) and Ras homolog gene family member A (RhoA) activities were analyzed by pull‑down assays. IL‑17‑CM significantly enhanced tube formation and increased the migration distance in CECs in comparison with CM. This effect was diminished by neutralizing C‑C motif chemokine 2 (CCL2) and C‑X‑C motif chemokine ligand 8 (CXCL8) expression in IL‑17‑CM, with a concomitant downregulation of Rac1 and RhoA activity in CECs. In conclusion, it was demonstrated that IL‑17 mediated the expression of CCL2 and CXCL8 in RPE cells, resulting in increased migration and tube formation in human CECs.