Demonstration of increased toll-like receptor 2 and toll-like receptor 4 expression in monocytes of type 1 diabetes mellitus patients with microvascular complications.
Type 1 diabetes mellitus (T1DM) is associated with increased microvascular complications and is a proinflammatory state. The toll-like receptors (TLRs) are pattern recognition receptors on monocytes and important in atherosclerosis. We have shown increased TLR2 and TLR4 expression on monocytes of T1DM compared with controls. In this report, we tested the surface expression of TLR2 and TLR4 on monocytes of T1DM patients with microvascular complications (T1DM-MV) compared with those without (T1DM) and healthy controls. The study was performed at the University of California Davis. Healthy controls (n = 31), T1DM patients (n = 31), and T1DM-MV patients (n = 34) were included. The TLR2 and TLR4 surface expression was significantly increased in T1DM-MV monocytes compared with T1DM and controls (P < .01). In addition, nuclear factor κB activity and interleukin-1β release were significantly increased in monocytes from T1DM-MV compared with T1DM (P < .005). Thus, we make the novel observation that TLR2 and TLR4 expression and signaling are increased in T1DM-MV compared with T1DM and may contribute to the accentuated proinflammatory state and complications of T1DM.
Laboratory for Atherosclerosis and Metabolic Research, University of California, Davis, Medical Center, Sacramento, CA 95817, USA. sridevi.devaraj@ucdmc.ucdavis.edu
Sridevi
S
Devaraj
Ishwarlal
I
Jialal
Jung-Mi
JM
Yun
Andrew
A
Bremer
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D003925:Diabetic Angiopathies / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood; D008297:Male; D055806:Microvessels / Q000378:metabolism; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D016328:NF-kappa B / Q000032:analysis; D051195:Toll-Like Receptor 2 / Q000032:analysis / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000032:analysis / Q000378:metabolism*; D055815:Young Adult
D001786:Blood Glucose; D002097:C-Reactive Protein; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005230:Fatty Acids, Nonesterified; D006442:Glycated Hemoglobin; D053583:Interleukin-1beta; D016328:NF-kappa B; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C517652:hemoglobin A1c protein, human