Author:
Cano-Cano Fátima,Alcalde-Estévez Elena,Gómez-Jaramillo 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.
Abstract
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.
Funder
Instituto de Salud Carlos III
Consejería de Salud y Familias, Junta de Andalucía
Ministerio de Economía, Industria y Competitividad, Gobierno de España
Comunidad de Madrid
Subject
Immunology,Immunology and Allergy
Cited by
17 articles.
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