Increased levels of ligands of Toll-like receptors 2 and 4 in type 1 diabetes

S. Devaraj, M. R. Dasu, S. H. Park, I. Jialal

Research output: Contribution to journalArticle

109 Scopus citations

Abstract

Type 1 diabetes is a proinflammatory state characterised by increased levels of circulating biomarkers of inflammation and monocyte activity. We have shown increased Toll-like receptor 2 (TLR2) and TLR4 expression and signalling in monocytes from type 1 diabetic patients. Several endogenous ligands of TLR2 and TLR4 have been identified; however, there is a paucity of data on levels of these endogenous ligands in diabetes. Thus, the aim of this study was to examine circulating levels of exogenous/endogenous ligands of TLR2 and TLR4 in type 1 diabetic patients and to compare these with the levels in matched healthy controls. Healthy controls (n∈=∈37) and type 1 diabetic patients (n∈=∈34) were recruited, and a fasting blood sample was obtained. Circulating levels of endotoxin, heat-shock protein 60 (Hsp60), high-mobility group box 1 (HMGB1) and growth arrest-specific 6 (GAS6) proteins were assessed by ELISA, and TLR2 and TLR4 expression was determined by flow cytometry. Levels of the classical TLR4 ligand, endotoxin, were significantly elevated in type 1 diabetic patients compared with those in matched controls. Hsp60 and HMGB1 concentrations were also significantly increased in the patients (p∈<∈0.01 and p∈<∈0.001, respectively). No significant differences were observed in GAS6. We report the novel observation that levels of ligands of TLR2 and TLR4 are significantly elevated in type 1 diabetes, and this, in concert with hyperglycaemia, accounts for the increase in TLR2 and TLR4 activity, underscoring the proinflammatory state of type 1 diabetes.

Original languageEnglish (US)
Pages (from-to)1665-1668
Number of pages4
JournalDiabetologia
Volume52
Issue number8
DOIs
StatePublished - Aug 2009

Keywords

  • Endotoxin
  • HMGB1
  • Hsp60
  • Inflammation
  • Ligand
  • Toll-like receptor

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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