{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T09:06:05Z","timestamp":1779959165488,"version":"3.53.1"},"reference-count":42,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondi Ateneo-UCSC","award":["2022"],"award-info":[{"award-number":["2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background: The retinal pigment epithelium (RPE) plays a pivotal role in the visual process by maintaining the blood\u2013retina barrier, protecting the retina from oxidative stress, and regulating immune responses. Consequently, dysfunction or degeneration of the RPE is implicated in a broad spectrum of retinal disorders that lead to progressive and irreversible vision loss. In this context, inflammation of the RPE has emerged as a critical factor in the pathogenesis of retinal degenerative diseases, underscoring its dual role as both a target and mediator of retinal inflammatory processes within the retina. Objectives: This study aims to preliminarily investigate, mainly by assessment of proinflammatory cytokine gene expression and immunoblotting, the molecular mechanisms underlying RPE inflammation induced by interactions between the RPE and microglia of the central nervous system. Methods\/Results: Using in vitro models of human RPE cells, the ARPE 19 cell line was exposed to conditioned media from microglia (CHME-5 cell line) under basal and proinflammatory conditions. We observed increased activation of the MAPK signaling pathway, (evidenced by a 4-fold increase in the phosphorylation ratio of MEK and ERK) alongside elevated expression of proinflammatory cytokines, assessed by RT-PCR and immunoblotting, and a 2-fold increase in reactive oxygen species levels in RPE cells, evaluated by colorimetric assays, after exposure with conditioned media. Specifically, IL-1\u03b2 and IL-8 levels increased more than 40-fold, while IL-6 expression showed a 4-fold increase compared to controls. Conclusions: These findings emphasize the central role of the RPE in retinal inflammation and suggest potential therapeutic targets to modulate immune responses and preserve retinal function.<\/jats:p>","DOI":"10.3390\/brainsci16060568","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T08:00:36Z","timestamp":1779955236000},"page":"568","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Retinal Pigment Epithelium Cell Line ARPE-19 Exposed to M1 Microglia Releases Proinflammatory Cytokines and Reactive Oxygen Species Through MAP-Kinase Pathway"],"prefix":"10.3390","volume":"16","author":[{"given":"Michela","family":"Pizzoferrato","sequence":"first","affiliation":[{"name":"Pharmacology Section, Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1694-1062","authenticated-orcid":false,"given":"Benedetto","family":"Falsini","sequence":"additional","affiliation":[{"name":"Macula & Genoma Foundation, 00133 Rome, Italy"},{"name":"Scientific Commettee, Universit\u00e0 Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1030-9429","authenticated-orcid":false,"given":"Giuseppe","family":"Tringali","sequence":"additional","affiliation":[{"name":"Pharmacology Section, Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierluigi","family":"Navarra","sequence":"additional","affiliation":[{"name":"Pharmacology Section, Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1397-2426","authenticated-orcid":false,"given":"Lucia","family":"Lisi","sequence":"additional","affiliation":[{"name":"Pharmacology Section, Department of Translational Medicine and Surgery, Universit\u00e0 Cattolica del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Jurga, A.M., Paleczna, M., and Kuter, K.Z. (2020). 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