Cano Cano, FátimaAlcalde Estévez, ElenaGómez Jaramillo, LauraIturregui, MartaSánchez Fernández, Elena MatildeGarcía Fernández, José ManuelOrtiz Mellet, CarmenCampos Caro, AntonioLópez Tinoco, Cristina2021-04-082021-04-082021Cano Cano, F., Alcalde Estévez, ., Gómez Jaramillo, L., Iturregui, M., Sánchez Fernández, E.M., García Fernández, J.M.,...,López Tinoco, C. (2021). Anti-Inflammatory (M2) Response Is Induced by a sp2-Iminosugar Glycolipid Sulfoxide in Diabetic Retinopathy. Frontiers in immunology, 12, 632132.1664-3224https://hdl.handle.net/11441/106812Diabetic retinopathy (DR) is one of the most common complications of Diabetes Mellitus (DM) and is directly associated with inflammatory processes. Currently, neuro-inflammation is considered an early event in DR and proceeds via microglia polarization. A hallmark of DR is the presence of retinal reactive gliosis. Here we report the beneficial effect of (S S,1R)-1-docecylsulfiny-5N,6O-oxomethylidenenojirimycin ((Ss)-DS-ONJ), a member of the sp2-iminosugar glycolipid (sp2-IGL) family, by decreasing iNOS and inflammasome activation in Bv.2 microglial cells exposed to pro-inflammatory stimuli. Moreover, pretreatment with (Ss)-DS-ONJ increased Heme-oxygenase (HO)-1 as well as interleukin 10 (IL10) expression in LPS-stimulated microglial cells, thereby promoting M2 (anti-inflammatory) response by the induction of Arginase-1. The results strongly suggest that this is the likely molecular mechanism involved in the anti-inflammatory effects of (S S)-DS-ONJ in microglia. (S S)-DS-ONJ further reduced gliosis in retinal explants from type 1 diabetic BB rats, which is consistent with the enhanced M2 response. In conclusion, targeting microglia polarization dynamics in M2 status by compounds with anti-inflammatory activities offers promising therapeutic interventions at early stages of DR.application/pdf14 p.engAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/sp2-iminosugar glycolipidsdiabetic retinopathymicrogliaimmunomodulationM2 responseinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccesshttps://doi.org/10.3389/fimmu.2021.632132