Anti-Inflammatory (M2) Response Is Induced by a sp(2)-Iminosugar Glycolipid Sulfoxide in Diabetic Retinopathy
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Author/sCano-Cano, Fátima; Alcalde-Estévez, Elena; Gómez Jaramillo, María Laura; Iturregui, Marta; Sánchez-Fernández, Elena M.; García-Fernández, José M.; Ortiz Mellet, Carmen; Campos Caro, Antonio; López-Tinoco, Cristina; Aguilar Diosdado, Manuel; Valverde, Ángela M.; Arroba, Ana I.
DepartmentBiomedicina, Biotecnología y Salud Pública; Medicina
SourceFront. Immunol. 12:632132
Diabetic 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 sp(2)-iminosugar glycolipid (sp(2)-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.