PMID- 29363728 OWN - NLM STAT- MEDLINE DCOM- 20180814 LR - 20211022 IS - 1791-3004 (Electronic) IS - 1791-2997 (Linking) VI - 17 IP - 3 DP - 2018 Mar TI - Interleukin-17 induces angiogenesis in vitro via CXCL8 and CCL2 in retinal pigment epithelium. PG - 4627-4632 LID - 10.3892/mmr.2018.8460 [doi] AB - 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 in vitro. 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. FAU - Chen, Ying AU - Chen Y AD - Department of Ophthalmology, First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing 400016, P.R. China. FAU - Zhong, Murui AU - Zhong M AD - Department of Ophthalmology, 452 Hospital of People's Liberation Army, Chengdu, Sichuan 610065, P.R. China. FAU - Yuan, Gangxiang AU - Yuan G AD - Department of Ophthalmology, First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing 400016, P.R. China. FAU - Peng, Hui AU - Peng H AD - Department of Ophthalmology, First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing 400016, P.R. China. LA - eng PT - Journal Article DEP - 20180118 PL - Greece TA - Mol Med Rep JT - Molecular medicine reports JID - 101475259 RN - 0 (Antibodies, Neutralizing) RN - 0 (Chemokine CCL2) RN - 0 (Culture Media, Conditioned) RN - 0 (Interleukin-17) RN - 0 (Interleukin-8) RN - 0 (Vascular Endothelial Growth Factor A) RN - EC 3.6.5.2 (rac1 GTP-Binding Protein) RN - EC 3.6.5.2 (rhoA GTP-Binding Protein) SB - IM MH - Antibodies, Neutralizing/immunology MH - Cell Movement/drug effects MH - Cell Proliferation/drug effects MH - Cells, Cultured MH - Chemokine CCL2/immunology/*metabolism MH - Choroid/cytology/metabolism MH - Culture Media, Conditioned/pharmacology MH - Enzyme-Linked Immunosorbent Assay MH - Humans MH - Interleukin-17/*pharmacology MH - Interleukin-8/immunology/*metabolism MH - Neovascularization, Physiologic/*drug effects MH - Retinal Pigment Epithelium/cytology/drug effects/metabolism MH - Vascular Endothelial Growth Factor A/analysis MH - rac1 GTP-Binding Protein/metabolism MH - rhoA GTP-Binding Protein/metabolism OTO - NOTNLM OT - retinal pigment epithelium OT - choroidal endothelial cell OT - neovascularization OT - C‑C motif chemokine ligand 2 OT - C‑X‑C motif chemokine ligand 8 EDAT- 2018/01/25 06:00 MHDA- 2018/08/15 06:00 CRDT- 2018/01/25 06:00 PHST- 2017/06/06 00:00 [received] PHST- 2017/11/30 00:00 [accepted] PHST- 2018/01/25 06:00 [pubmed] PHST- 2018/08/15 06:00 [medline] PHST- 2018/01/25 06:00 [entrez] AID - 10.3892/mmr.2018.8460 [doi] PST - ppublish SO - Mol Med Rep. 2018 Mar;17(3):4627-4632. doi: 10.3892/mmr.2018.8460. Epub 2018 Jan 18.