RT info:eu-repo/semantics/article T1 Predominantly pro-inflammatory phenotype with mixed M1/M2 polarization of peripheral blood classical monocytes and monocyte-derived macrophages among patients with excessive ethanol intake A1 Fernández Regueras, María A1 Carbonell, Cristina A1 Salete Granado, Daniel A1 García, Juan Luis A1 Gragera, Marcos A1 Pérez Nieto, María Ángeles A1 Morán Plata, Francisco Javier A1 Mayado, Andrea A1 Torres, Jorge Luis A1 Corchete Sánchez, Luis Antonio A1 Usategui Martín, Ricardo A1 Bueno Martínez, Elena A1 Rojas Pirela, Maura A1 Sabio, Guadalupe A1 González Sarmiento, Rogelio A1 Orfao, Alberto A1 Laso, Francisco Javier A1 Almeida, Julia A1 Marcos, Miguel K1 Alcohol Use Disorders K1 Excessive alcohol drinkers K1 Monocyte/macrophage phenotype K1 M1 K1 M2 K1 Innate immunity K1 Flow cytometry K1 MicroRNA K1 6113.01 Alcoholismo K1 2412 Inmunología K1 2415 Biología Molecular K1 2407 Biología Celular AB Excessive alcohol consumption impairs the immune system, induces oxidative stress, and triggers the activation of peripheral blood (PB) monocytes, thereby contributing to alcoholic liver disease (ALD). We analyzed the M1/M2 phenotypes of circulating classical monocytes and macrophage-derived monocytes (MDMs) in excessive alcohol drinkers (EADs). PB samples from 20 EADs and 22 healthy controls were collected for isolation of CD14+ monocytes and short-term culture with LPS/IFNγ, IL4/IL13, or without stimulation. These conditions were also used to polarize MDMs into M1, M2, or M0 phenotypes. Cytokine production was assessed in the blood and culture supernatants. M1/M2-related markers were analyzed using mRNA expression and surface marker detection. Additionally, the miRNA profile of CD14+ monocytes was analyzed. PB samples from EADs exhibited increased levels of pro-inflammatory cytokines. Following short-term culture, unstimulated blood samples from EADs showed higher levels of soluble TNF-α and IL-8, whereas monocytes expressed increased levels of surface TNF-α and elevated mRNA expression of pro-inflammatory cytokines and inducible nitric oxide synthase. MDMs from EADs showed higher levels of TNF-α and CD206 surface markers and increased IL-10 production. LPS/IFNγ induced higher mRNA expression of Nrf2 only in the controls. miRNA analysis revealed a distinctive miRNA profile that is potentially associated with liver carcinogenesis and ALD through inflammation and oxidative stress. This study confirms the predominantly pro-inflammatory profile of PB monocytes among EADs and suggests immune exhaustion features in MDMs. PB MDPI SN 2076-3921 YR 2023 FD 2023 LK https://uvadoc.uva.es/handle/10324/67727 UL https://uvadoc.uva.es/handle/10324/67727 LA eng NO Antioxidants, 2023, Vol. 12, Nº. 9, 1708 NO Producción Científica DS UVaDOC RD 24-nov-2024