{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T23:55:19Z","timestamp":1793663719986,"version":"4.5.1"},"reference-count":57,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,10,24]],"date-time":"2011-10-24T00:00:00Z","timestamp":1319414400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2012,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chronic inflammation is implicated in the pathogenesis of age\u2010related macular degeneration (AMD). Choroidal neovascularization (CNV) observed in exudative form of AMD results in vision loss. Human retinal pigment epithelial cell (HRPE) layer and choroidal tissue are the primary pathological sites in AMD. Pathological and therapeutic evidences have strongly indicated the vascular endothelial growth factor (VEGF) molecules as critical components in CNV pathogenesis. In these studies, we used human primary HRPE and choroidal fibroblast cells (HCHF) prepared from adult donor eyes. The effects of inflammatory cytokine (IFN\u2010\u03b3\u2009+\u2009TNF\u2010\u03b1\u2009+\u2009IL\u20101\u03b2) mix (ICM) on global gene expression profiles in HRPE cells, revealed 10\u2010 and 9\u2010fold increase in VEGF\u2010A and VEGF\u2010C expression, respectively. The microarray results were validated by quantitative RT\u2010PCR and secretion of VEGFs proteins. IL\u20101\u03b2 is the most potent in inducing VEGFs secretion followed by IFN\u2010\u03b3 and TNF\u2010\u03b1, and the secretion was more effective in the presence of 2 and 3 cytokines. NF\u2010\u03baB and JAK\u2010STAT pathway, but not HIF\u20101\u03b1, Sp\u20101, Sp\u20103, and STAT\u20103, transcription factors were upregulated and translocated to nucleus by ICM treatment. The mRNA levels of VEGF\u2010A and VEGF\u2010C and secretion of these proteins were also significantly enhanced by ICM in HCHF cells. The secretion of other angiogenic molecules, PEDF, SDF\u20101\u03b1, endostatin, and angiopoietins was not affected by ICM. Our results show that the inflammatory cytokines enhance secretion of VEGF\u2010A and VEGF\u2010C by HRPE and HCHF cells. These studies indicate that VEGFs secreted by these cells initiate and promote pathological choroidal and retinal noevascularization processes in AMD. J. Cell. Physiol. 227: 116\u2013126, 2012. \u00a9 2011 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jcp.22708","type":"journal-article","created":{"date-parts":[[2011,3,3]],"date-time":"2011-03-03T21:11:34Z","timestamp":1299186694000},"page":"116-126","source":"Crossref","is-referenced-by-count":126,"title":["Regulation of VEGF expression in human retinal cells by cytokines: Implications for the role of inflammation in age\u2010related macular degeneration"],"prefix":"10.1002","volume":"227","author":[{"given":"Chandrasekharam N.","family":"Nagineni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay K.","family":"Kommineni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abitha","family":"William","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Detrick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.","family":"Hooks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,10,24]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199412013312203"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0039-6257(03)00030-4"},{"key":"e_1_2_6_4_1","first-page":"3178","article-title":"Growth factor localization in choroidal neovascular membranes of age\u2010related macular degeneration","volume":"35","author":"Amin R","year":"1994","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(02)01624-0"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2005.05.007"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0502819102"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006982-199414020-00006"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.4.9.1395"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000118600.91698.BB"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.40.25176"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.122.7.1013"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2003.08.001"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.survophthal.2005.12.001"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5390.946"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2006.01.013"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0603-669"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.58.061705.145635"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.3109\/02713689008999440"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.122.4.564"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(93)31466-1"},{"key":"e_1_2_6_22_1","first-page":"119","article-title":"Macrophage and retinal pigment epithelium expression of angiogenic cytokines in choroidal neovascularization","volume":"8","author":"Grossniklaus HE","year":"2002","journal-title":"Mol Vision"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.123.7.914"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1350-9462(01)00010-6"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0501536102"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1110359"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.6.3789"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00521.x"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2006.10.040"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.81.2.154"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2010.10.042"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-007-0749-4"},{"key":"e_1_2_6_33_1","first-page":"855","article-title":"Transdifferentiated retinal pigment epithelial cells are immunoreactive for vascular endothelial growth factor in surgically excised age\u2010related macular degeneration\u2010related choroidal neovascular membranes","volume":"37","author":"Lopez PF","year":"1996","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_6_34_1","volume-title":"The retinal pigment epithelium, function and disease","author":"Marmor MF","year":"1998"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)61231-X"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-003-0838-y"},{"key":"e_1_2_6_37_1","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1128\/cdli.1.5.569-577.1994","article-title":"Synergistic effects of gamma interferon on inflammatory mediators that induce interleukin\u20106 gene expression and secretion by human retinal pigment epithelial cells","volume":"1","author":"Nagineni CN","year":"1994","journal-title":"Clin Diagn Lab Immunol"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1006\/cyto.1996.0083"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.10378"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.20213"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.20839"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1955"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2007.06.005"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0408835103"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2007.06.025"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1350-9462(00)00025-2"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2008.05.001"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003554"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.125.3.300"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.291.6.704"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00021.2004"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.9.081307.164350"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)99049-6"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03987"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2007.06.013"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/0039-6257(87)90115-9"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.122.4.598"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2006.09.002"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.22708","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.22708","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T07:36:56Z","timestamp":1696923416000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.22708"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,10,24]]},"references-count":57,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2012,1]]}},"alternative-id":["10.1002\/jcp.22708"],"URL":"https:\/\/doi.org\/10.1002\/jcp.22708","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,10,24]]}}}