Endocrine Abstracts (2017) 49 GP82 | DOI: 10.1530/endoabs.49.GP82

Reduced level of soluble TLR2 in type 2 diabetes despite increased TLR2 monocyte expression

Emanuela Zaharieva1, Tsvetelina Velikova2, Elena Vikentieva3, Dora Popova3, Adelina Tsakova4 & Zdravko Kamenov1

1Medical University Sofia, Alexandrovska University Hospital, Clinic of Endocrinology, Sofia, Bulgaria; 2Medical University Sofia, St Ivan Rilski University Hospital, Laboratory of Clinical Immunology, Sofia, Bulgaria; 3Military Medical Academy, Department of Clinical Laboratory and Immunology, Sofia, Bulgaria; 4Medical University Sofia, Alexandrovska University Hospital, Central Clinical Laboratory, Sofia, Bulgaria.

Background: Chronic low-grade inflammation is a major factor in the pathogenesis of type 2 diabetes. One way for promoting inflammatory cytokines secretion is through activation of toll-like receptors (TLR). Their overexpression on monocytes has been demonstrated in insulin resistance and type 2 diabetes. Soluble forms of toll-like receptors (sTLR) are considered a regulatory mechanisms of their activation. Their role has been described in modulation of bacteria-induced infective diseases but has not been analysed in diabetes. The aim of the study was to evaluate the place of sTLR2 in type 2 diabetes and compare it with monocyte expression.

Subjects and methods: We performed a cross-sectional study that included 63 patients with type 2 diabetes and 25 controls. All were assayed for soluble forms of TLR2 through Enzyme-Linked Immunosorbent Assay. We evaluated monocyte expression of TLR2 in 28 diabetic patients and 14 control subjects through direct immunofluorescence with conjugated monoclonal antibodies. All participants were assayed for Interleukin 6 (IL-6) through Electro-Chemiluminescence Immunoassay and high sensitivity C-reactive protein (hs-CRP) through Particle Enhanced Immunoturbidimetric Assay.

Results: TLR2 expression in patients with type 2 diabetes was higher compared to controls (89.85±9.66% vs. 50.20±36.91% for CD14++CD16+ monocytes, P=0.003 and 34.54±12.38% vs. 17.12±15.39%, P=0.011 for CD14+CD16++ monocytes) but sTLR2 was significantly lower in diabetic subjects (1.15±0.65 ng/ml vs 1.44±0.60 ng/ml, P=0.019). Inflammatory status between groups was confirmed significantly different concerning hs-CRP (2.79±2.89 mg/l vs. 0.70±0.89 mg/l, P=0.000) and IL6 (2.65±2.46 ng/ml vs 1.44±0.22 ng/ml, P=0.005) with higher values in diabetic group, although correlations with TLR2 expression were not established (P>0.05).

Conclusion: Type 2 diabetes-associated chronic inflammatory state is characterised by elevated monocyte expression of TLR2 but decreased serum sTLR2 level. This poses the question about presence of an impaired immunomodulation of TLRs’ activation in diabetes.

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