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. 

TITLE=Anti-Inflammatory (M2) Response Is Induced by a sp2-Iminosugar Glycolipid Sulfoxide in Diabetic Retinopathy

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.632132

DOI=10.3389/fimmu.2021.632132

ISSN=1664-3224

ABSTRACT=<p>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 <italic>via</italic> microglia polarization. A hallmark of DR is the presence of retinal reactive gliosis. Here we report the beneficial effect of (<italic>S</italic><sub>S</sub>,1<italic>R</italic>)-1-docecylsulfiny-5<italic>N</italic>,6<italic>O</italic>-oxomethylidenenojirimycin ((<italic>Ss</italic>)-DS-ONJ), a member of the sp<sup>2</sup>-iminosugar glycolipid (sp<sup>2</sup>-IGL) family, by decreasing iNOS and inflammasome activation in Bv.2 microglial cells exposed to pro-inflammatory stimuli. Moreover, pretreatment with (<italic>Ss</italic>)-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 (<italic>S</italic><sub>S</sub>)-DS-ONJ in microglia. (<italic>S</italic><sub>S</sub>)-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.</p>