%0 Journal Article 
%A Cano-Cano, Fátima
%A Alcalde-Estévez, Elena
%A Gómez Jaramillo, María Laura
%A Iturregui, Marta
%A Sánchez-Fernández, Elena M.
%A García-Fernández, José M.
%A Ortiz Mellet, Carmen
%A Campos Caro, Antonio
%A López Tinoco, Cristina
%A Aguilar Diosdado, Manuel
%A Valverde, Ángela M.
%A Arroba Espinosa, Ana Isabel
%T Anti-Inflammatory (M2) Response Is Induced by a sp(2)-Iminosugar Glycolipid Sulfoxide in Diabetic Retinopathy
%D 2021
%@ 1664-3224
%U http://hdl.handle.net/10498/24795
%X 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.
%K sp(2)-iminosugar glycolipids
%K diabetic retinopathy
%K microglia
%K immunomodulation
%K M2 response
%~ Universidad de Cádiz