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The purpose of the study was to evaluate whether the selective \u03b21-adrenoreceptor (\u03b21-AR) antagonist metoprolol could modulate the inflammatory response to hyperglycemic conditions. For this purpose, human retinal endothelial cells (HREC) were treated with normal (5 mM) or high glucose (25 mM, HG) in the presence of metoprolol (10 \u03bcM), epinephrine (1 \u03bcM), or both compounds. Metoprolol prevented both the HG-induced reduction of cell viability (MTT assays) and the modulation of the angiogenic potential of HREC (tube formation assays) reducing the TNF-\u03b1, IL-1\u03b2, and VEGF mRNA levels (qRT-PCR). Moreover, metoprolol prevented the increase in phospho-ERK1\/2, phospho-cPLA2, COX2, and protein levels (Western blot) as well as counteracting the translocation of ERK1\/2 and cPLA2 (high-content screening). Metoprolol reduced ROS accumulation in HG-stimulated HREC by activating the anti-oxidative cellular response mediated by the Keap1\/Nrf2\/HO-1 pathway. In conclusion, metoprolol exerted a dual effect on HG-stimulated HREC, decreasing the activation of the pro-inflammatory ERK1\/2\/cPLA2\/COX2 axis, and counteracting ROS accumulation by activating the Keap1\/Nrf2\/HO-1 pathway.<\/jats:p>","DOI":"10.3390\/cells11010051","type":"journal-article","created":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T01:00:54Z","timestamp":1640566854000},"page":"51","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The Anti-Inflammatory Effect of the \u03b21-Adrenergic Receptor Antagonist Metoprolol on High Glucose Treated Human Microvascular Retinal Endothelial Cells"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4855-8615","authenticated-orcid":false,"given":"Giovanni","family":"Giurdanella","sequence":"first","affiliation":[{"name":"Biochemistry Section, Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Longo","sequence":"additional","affiliation":[{"name":"Biochemistry Section, Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3323-9344","authenticated-orcid":false,"given":"Alfio","family":"Distefano","sequence":"additional","affiliation":[{"name":"Biochemistry Section, Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melania","family":"Olivieri","sequence":"additional","affiliation":[{"name":"U.O. 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