DHA Inhibited AGEs-Induced Retinal Microglia Activation Via Suppression of the PPARγ/NFκB Pathway and Reduction of Signal Transducers in the AGEs/RAGE Axis Recruitment into Lipid Rafts

摘要: Recent studies revealed that dietary intake of docosahexaenoic acid (DHA) prevented diabetic retinopathy (DR), but the underlying mechanism was not fully understood. Retinal microglia are a specialized population macrophages in retina. Considerable evidence has shown activation may trigger neuronal death and vascular dysfunction DR. The aim this study to investigate effects DHA on advanced glycation end products (AGEs)-induced using an vitro culture system, concurrently explore mediating mechanisms. inhibited AGEs-induced tumor necrosis factor α (TNFα) secretion. These were directly linked with suppression nuclear factor-kappa B (NFκB) activity, as evident by reduction p-IκBα expression, p-NFκB p65 nucleus translocation, NFκB DNA binding regulation gene transcription (TNFα, IL-1β, ICAM-1, RAGE mRNA). Furthermore, significantly increased phosphorylation peroxisome proliferator-activated receptor-gamma (PPARγ), combined PPARγ stealth RNAi oligonucleotide, we confirmed inhibition partially through PPARγ/NFκB pathway. Moreover, although AGEs incubation dramatically elevated expression cell surface receptor for (RAGE), Src recruitment into lipid rafts. AGEs–RAGE axis downstream signal transducers mitogen-activated protein kinase (p38 JNK) phosphorylation. Taken together, might inhibit via pathway, AGEs/RAGE transducer results provide novel potential anti-inflammatory DR prevention.