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Anti-Inflammatory (M2) Response Is Induced by a sp(2)-Iminosugar Glycolipid Sulfoxide in Diabetic Retinopathy

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 re...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013727/
https://www.ncbi.nlm.nih.gov/pubmed/33815384
http://dx.doi.org/10.3389/fimmu.2021.632132
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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.
author_facet 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.
author_sort Cano-Cano, Fátima
collection PubMed
description 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.
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spelling pubmed-80137272021-04-02 Anti-Inflammatory (M2) Response Is Induced by a sp(2)-Iminosugar Glycolipid Sulfoxide in Diabetic Retinopathy 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. Front Immunol Immunology 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. Frontiers Media S.A. 2021-03-18 /pmc/articles/PMC8013727/ /pubmed/33815384 http://dx.doi.org/10.3389/fimmu.2021.632132 Text en Copyright © 2021 Cano-Cano, Alcalde-Estévez, Gómez-Jaramillo, Iturregui, Sánchez-Fernández, García Fernández, Ortiz Mellet, Campos-Caro, López-Tinoco, Aguilar-Diosdado, Valverde and Arroba http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
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.
Anti-Inflammatory (M2) Response Is Induced by a sp(2)-Iminosugar Glycolipid Sulfoxide in Diabetic Retinopathy
title Anti-Inflammatory (M2) Response Is Induced by a sp(2)-Iminosugar Glycolipid Sulfoxide in Diabetic Retinopathy
title_full Anti-Inflammatory (M2) Response Is Induced by a sp(2)-Iminosugar Glycolipid Sulfoxide in Diabetic Retinopathy
title_fullStr Anti-Inflammatory (M2) Response Is Induced by a sp(2)-Iminosugar Glycolipid Sulfoxide in Diabetic Retinopathy
title_full_unstemmed Anti-Inflammatory (M2) Response Is Induced by a sp(2)-Iminosugar Glycolipid Sulfoxide in Diabetic Retinopathy
title_short Anti-Inflammatory (M2) Response Is Induced by a sp(2)-Iminosugar Glycolipid Sulfoxide in Diabetic Retinopathy
title_sort anti-inflammatory (m2) response is induced by a sp(2)-iminosugar glycolipid sulfoxide in diabetic retinopathy
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013727/
https://www.ncbi.nlm.nih.gov/pubmed/33815384
http://dx.doi.org/10.3389/fimmu.2021.632132
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