Devaraj S, Dasu M R, Park S H, Jialal I
Laboratory for Atherosclerosis and Metabolic Research, UC Davis Medical Center, Sacramento, CA 95817, USA.
Diabetologia. 2009 Aug;52(8):1665-8. doi: 10.1007/s00125-009-1394-8. Epub 2009 May 20.
AIMS/HYPOTHESIS: 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.
CONCLUSIONS/INTERPRETATION: 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.
目的/假设：1型糖尿病是一种促炎状态，其特征为循环炎症生物标志物和单核细胞活性水平升高。我们已表明1型糖尿病患者单核细胞中Toll样受体2（TLR2）和TLR4的表达及信号传导增加。已鉴定出TLR2和TLR4的几种内源性配体；然而，关于糖尿病中这些内源性配体水平的数据却很少。因此，本研究的目的是检测1型糖尿病患者中TLR2和TLR4的外源性/内源性配体的循环水平，并将其与匹配的健康对照者的水平进行比较。
招募健康对照者（n = 37）和1型糖尿病患者（n = 34），采集空腹血样。通过酶联免疫吸附测定法评估内毒素、热休克蛋白60（Hsp60）、高迁移率族蛋白B1（HMGB1）和生长停滞特异性蛋白6（GAS6）的循环水平，并通过流式细胞术测定TLR2和TLR4的表达。
与匹配的对照组相比，1型糖尿病患者中经典TLR4配体内毒素的水平显著升高。患者体内Hsp60和HMGB1的浓度也显著增加（分别为p < 0.01和p < 0.001）。GAS6未观察到显著差异。
结论/解读：我们报告了一项新发现，即1型糖尿病中TLR2和TLR4配体水平显著升高，这与高血糖共同导致TLR2和TLR4活性增加，突出了1型糖尿病的促炎状态。
