O-GlcNAcylation and inflammation: A vast territory to explore

Abstract

O-GlcNAcylation is a reversible post-translational modification that regulates the activities of cytosolic and nuclear proteins according to glucose availability. This modification appears to participate in several hyperglycemia-associated complications. An important feature of metabolic diseases such as diabetes and obesity is the presence of a low-grade chronic inflammation that causes numerous complications. Hyperglycemia associated with the metabolic syndrome is known to promote inflammatory processes through different mechanisms including oxidative stress and abnormally elevated protein O-GlcNAcylation. However, the role of O-GlcNAcylation on inflammation remains contradictory. OGlcNAcylation associated with hyperglycemia has been shown to increase NF?B transcriptional activity through different mechanisms. This could contribute in inflammationassociated diabetic complications. However, in other conditions such as acute vascular injury, O-GlcNAc also exerts anti-inflammatory effects via inhibition of the NF?B pathway, suggesting a complex regulation of inflammation by O-GlcNAc. Moreover, whereas macrophages and monocytes exposed to high glucose for a long term period developed a proinflammatory phenotype, the impact of O-GlcNAcylation in these cells remains unclear. A future challenge will be to clearly establish the role of O-GlcNAcylation in pro- and antiinflammatory functions in macrophages.