Cano-Cano, FatimaAlcalde-Estevez, ElenaGomez-Jaramillo, LauraIturregui, MartaSánchez-Fernandez, Elena MGarcia Fernandez, Jose MOrtiz Mellet, CarmenCampos-Caro, AntonioLopez-Tinoco, CristinaAguilar-Diosdado, ManuelValverde, Angela MArroba, Ana I2023-02-092023-02-092021-03-01Cano-Cano F, Alcalde-Estévez E, Gómez-Jaramillo L, Iturregui M, Sánchez-Fernández EM, García Fernández JM, et al. Anti-Inflammatory (M2) Response Is Induced by a sp2-Iminosugar Glycolipid Sulfoxide in Diabetic Retinopathy. Front Immunol. 2021 Mar 18;12:632132http://hdl.handle.net/10668/17531Diabetic 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 (SS,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 (SS)-DS-ONJ in microglia. (SS)-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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/M2 responseDiabetic retinopathyImmunomodulationMicrogliasp2-iminosugar glycolipidsAnimalsAnti-inflammatory agentsCytokinesDiabetic retinopathyGliosisGlycolipidsInflammasomesInflammationLipopolysaccharidesMicrogliaNitric oxide synthase type IIRatsRetinaSignal transductionSulfoxidesresearch article33815384open accessAntiinflamatoriosCitocinasGlucolípidosInflamaciónInflamasomasLipopolisacáridosMicroglíaRetinopatía diabética10.3389/fimmu.2021.6321321664-3224PMC8013727https://www.frontiersin.org/articles/10.3389/fimmu.2021.632132/pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013727/pdf