%0 Journal Article
%A Cano-Cano, Fatima
%A Alcalde-Estevez, Elena
%A Gomez-Jaramillo, Laura
%A Iturregui, Marta
%A Sánchez-Fernandez, Elena M
%A Garcia Fernandez, Jose M
%A Ortiz Mellet, Carmen
%A Campos-Caro, Antonio
%A Lopez-Tinoco, Cristina
%A Aguilar-Diosdado, Manuel
%A Valverde, Angela M
%A Arroba, Ana I
%T Anti-Inflammatory (M2) Response Is Induced by a sp2-Iminosugar Glycolipid Sulfoxide in Diabetic Retinopathy.
%D 2021
%U http://hdl.handle.net/10668/17531
%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 (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.
%K M2 response
%K Diabetic retinopathy
%K Immunomodulation
%K Microglia
%K sp2-iminosugar glycolipids
%~