PMID- 27419340 OWN - NLM STAT- MEDLINE DCOM- 20171204 LR - 20220321 IS - 1460-2202 (Electronic) IS - 0271-3683 (Linking) VI - 42 IP - 3 DP - 2017 Mar TI - Interleukin (IL)-17A Promotes Angiogenesis in an Experimental Corneal Neovascularization Model. PG - 368-379 LID - 10.1080/02713683.2016.1196705 [doi] AB - PURPOSE: To explore the roles of interleukin (IL)-17A in alkali-induced corneal neovascularization (CRNV). METHODS: Induction of CRNV by alkali injury was performed and compared in recombinant mouse IL-17A protein or anti-mouse IL-17A neutralizing antibody (Ab)-treated mice. The expression of IL-17A, IL-17A receptor (IL-17RA), vascular endothelial growth factor (VEGF), IL-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1) in burned corneas or other cells was examined by RT-PCR and western blot. The infiltration of macrophages, neutrophils, and c-Kit-positive progenitor cells into burned corneas was detected by flow cytometry (FCM). The Raw264.7 cell line and mouse corneal fibroblasts were stimulated by mouse recombinant IL-17A or anti-mouse IL-17A neutralizing Ab in vitro, and the expression of IL-6 and VEGF in culture supernatant was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: The alkali-induced CRNV peaked 2 weeks after the alkali burn. Compared with the vehicle-treated group, mouse recombinant IL-17A administration significantly increased the amount of CRNV, and it decreased in mice treated with neutralizing anti-mouse IL-17A Ab. RT-PCR and western blot confirmed that the IL-17A upregulated intracorneal VEGF, IL-6, IL-8, MCP-1, and phosphorylated focal adhesion kinase (pFAK) expression. FCM revealed that the infiltration of intracorneal progenitor cells, M1 macrophages, and neutrophils was also augmented in IL-17A-treated mice. The ELISA showed that IL-17A markedly induced VEGF and IL-6 expression in the Raw264.7 murine macrophage cell line and in the mouse corneal fibroblasts. CONCLUSIONS: IL-17A-treated mice exhibited enhanced alkali-induced CRNV through enhanced intracorneal progenitor cell and inflammatory cell infiltration, and increased VEGF and IL-6 expression by fibroblasts and macrophages. FAU - Liu, Gaoqin AU - Liu G AD - a Department of Ophthalmology , The First Affiliated Hospital of Soochow University , Suzhou , P.R. China. AD - b Jiangsu Clinical Immunology Institute, The First Affiliated Hospital of Soochow University , Suzhou , P.R. China. FAU - Wu, Hongya AU - Wu H AD - b Jiangsu Clinical Immunology Institute, The First Affiliated Hospital of Soochow University , Suzhou , P.R. China. FAU - Lu, Peirong AU - Lu P AD - a Department of Ophthalmology , The First Affiliated Hospital of Soochow University , Suzhou , P.R. China. AD - b Jiangsu Clinical Immunology Institute, The First Affiliated Hospital of Soochow University , Suzhou , P.R. China. FAU - Zhang, Xueguang AU - Zhang X AD - b Jiangsu Clinical Immunology Institute, The First Affiliated Hospital of Soochow University , Suzhou , P.R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160715 PL - England TA - Curr Eye Res JT - Current eye research JID - 8104312 RN - 0 (Alkalies) RN - 0 (Il17a protein, mouse) RN - 0 (Interleukin-17) RN - 0 (Recombinant Proteins) RN - 63231-63-0 (RNA) SB - IM MH - Alkalies/toxicity MH - Animals MH - Blotting, Western MH - Cell Line MH - Cornea/drug effects/metabolism/*pathology MH - Corneal Neovascularization/chemically induced/*drug therapy/genetics MH - Disease Models, Animal MH - Fibroblasts/drug effects/metabolism/pathology MH - Flow Cytometry MH - *Gene Expression Regulation MH - Immunohistochemistry MH - Interleukin-17/biosynthesis/*genetics/pharmacology MH - Male MH - Mice MH - Mice, Inbred BALB C MH - RNA/*genetics MH - Recombinant Proteins/pharmacology MH - Reverse Transcriptase Polymerase Chain Reaction OTO - NOTNLM OT - Chemokine OT - IL-17A OT - corneal OT - inflammation OT - neovascularization EDAT- 2016/07/16 06:00 MHDA- 2017/12/05 06:00 CRDT- 2016/07/16 06:00 PHST- 2016/07/16 06:00 [pubmed] PHST- 2017/12/05 06:00 [medline] PHST- 2016/07/16 06:00 [entrez] AID - 10.1080/02713683.2016.1196705 [doi] PST - ppublish SO - Curr Eye Res. 2017 Mar;42(3):368-379. doi: 10.1080/02713683.2016.1196705. Epub 2016 Jul 15.