title: Increased toll-like receptor (TLR) 2 and TLR4 expression in monocytes from patients with type 1 diabetes: further evidence of a proinflammatory state.
abstract: BACKGROUND
  Type 1 diabetes (T1DM) is associated with increased cardiovascular mortality. It is a pro-inflammatory state as evidenced by increased circulating biomarkers and monocyte activity. The toll-like receptors (TLRs) are pattern recognition receptors, expressed abundantly on monocytes. TLR2 and TLR4 are important in atherosclerosis. However, there is a paucity of data examining TLR2 and TLR4 expression in T1DM and examining its contribution to the proinflammatory state.
  
  
  OBJECTIVE
  Thus, we examined TLR2 and TLR4 expression in monocytes from T1DM patients compared with controls (n = 31 per group).
  
  
  METHODS
  The study was performed at the University of California Davis Medical Center.
  
  
  METHODS
  Healthy controls (n = 31) and T1DM patients (n = 31) were included in the study.
  
  
  RESULTS
  TLR2 and TLR4 surface expression and mRNA were significantly increased in T1DM monocytes compared with controls. Downstream targets of TLR, nuclear factor kappaB, myeloid differentiation factor 88, Trif, and phosphorylated IL-1 receptor-associated kinase were significantly up-regulated in T1DM. Finally, the release of IL-1beta and TNF-alpha was significantly increased in monocytes from T1DM compared with controls and correlated with TLR2 and TLR4 expression (P < 0.005). In addition, TLR2 and TLR4 expression was significantly correlated to glycosylated hemoglobin, carboxymethyllysine, and nuclear factor kappaB (P < 0.02).
  
  
  CONCLUSIONS
  Thus, we make the novel observation that TLR2 and TLR4 expression and signaling are increased in T1DM and contribute to the proinflammatory state.
authors.affiliation: Laboratory for Atherosclerosis and Metabolic Research, University of California Davis Medical Center, Sacramento, California 95817, USA.
authors.forename: Sridevi
authors.initials: S
authors.lastname: Devaraj
authors.forename: Mohan R
authors.initials: MR
authors.lastname: Dasu
authors.forename: Jason
authors.initials: J
authors.lastname: Rockwood
authors.forename: William
authors.initials: W
authors.lastname: Winter
authors.forename: Steven C
authors.initials: SC
authors.lastname: Griffen
authors.forename: Ishwarlal
authors.initials: I
authors.lastname: Jialal
mesh_terms: D000328:Adult; D015153:Blotting, Western; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D008297:Male; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D018709:Statistics, Nonparametric; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D012333:RNA, Messenger; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D053592:Interleukin-1 Receptor-Associated Kinases