High glucose and hyperglycemic sera from type 2 diabetic patients impair DC differentiation by inducing ROS and activating Wnt/β-catenin and p38 MAPK

Maria Saveria Gilardini Montani, Marisa Granato, Laura Cuomo, Sandro Valia, Livia Di Renzo, Gabriella D'Orazi, Alberto Faggioni, Mara Cirone

Research output: Contribution to journalArticle

Abstract

Type 2 is the type of diabetes with higher prevalence in contemporary time, representing about 90% of the global cases of diabetes. In the course of diabetes, several complications can occur, mostly due to hyperglycemia and increased reactive oxygen species (ROS) production. One of them is represented by an increased susceptibility to microbial infections and by a reduced capacity to clear them. Therefore, knowing the impact of hyperglycemia on immune system functionality is of utmost importance for the management of the disease. In this study, we show that medium containing high glucose reduced the in-vitro differentiation of monocytes into functional DCs and their activation mediated by PAMPs or DAMPs. Most importantly, the same effects were mediated by the hyperglycemic sera derived by type 2 diabetic patients, mimicking a more physiologic condition. DC dysfunction caused by hyperglycemia may be involved in the inefficient control of infections observed in diabetic patients, given the pivotal role of these cells in both the innate and adaptive immune response. Searching for the molecular mechanisms underlying DC dysfunction, we found that canonical Wnt/β-catenin and p38 MAPK pathways were activated in the DCs differentiated either in the presence of high glucose or of hyper-glycemic sera. Interestingly, the activation of these pathways and the DC immune dysfunction were partially counteracted by the anti-oxidant quercetin, a flavonoid already known to exert several beneficial effects in diabetes.

Original languageEnglish
Pages (from-to)805-813
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1862
Issue number4
DOIs
Publication statusPublished - Apr 1 2016

Keywords

  • DC
  • Hyperglycemia
  • P38 MAPK
  • Quercetin
  • ROS
  • Wnt/β-catenin

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine

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