Radzyukevich Yaroslav V, Kosyakova Ninel I, Prokhorenko Isabella R
Hospital of Pushchino Scientific Center, Russian Academy of Sciences, Pushchino 142290, Russia.
Department of Molecular Biomedicine, Institute of Basic Biological Problems, Federal Research Center "Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences", Pushchino 142290, Russia.
Life (Basel). 2023 Feb 16;13(2):550. doi: 10.3390/life13020550.
Epidemiological data indicate the active progression of various forms of diabetes mellitus in patients with bronchial asthma (BA), but little is known about the mechanisms of comorbidity formation. TLR2 and TLR4 are involved in the progression of asthma and type 2 diabetes mellitus (T2DM). These receptors are involved in the inflammatory response to Gram(+) and Gram(-) bacteria, respectively, so changes in their expression may affect the predisposition of patients to bacteremia. The aim of this study was to analyze the expression and functional activity of toll-like receptor 2 and 4 (TLR2 and TLR4) on peripheral blood cells of patients with BA, T2DM, and BA + T2DM. The expression of TLR2 and TLR4 was analyzed by flow cytometry. Whole blood samples were incubated with lipopolysaccharides from (LPS) and lipoteichoic acid from (LTA). The concentration of cytokines and soluble blood proteins was determined by ELISA. Patients with comorbid diseases showed a statistically significant increase in TLR2 expression on both monocytes and neutrophils compared with healthy donors and patients with BA. We found increased expression of TLR4 on the surface of blood monocytes from patients compared to donors. The activation of blood cells of patients and donors with LPS or LTA led to an increase in the expression of "fast" pro-inflammatory cytokines (TNF-α, IL-6). In patients with BA, the average production of TNF-α in response to endotoxin was two times higher than in other studied groups. The reactions of blood cells in patients with T2DM and BA + T2DM did not differ significantly. The expression and functional activity of TLR2 and TLR4 on the blood cells of patients with comorbid disease were similar to those only in patients with T2DM. The greatest increase in the synthesis of the pro-inflammatory cytokine TNF-α in response to LPS and LTA was observed in patients with BA, which can lead to an inadequate response to bacteremia.
流行病学数据表明支气管哮喘（BA）患者中各种形式的糖尿病呈活跃进展，但关于合并症形成的机制知之甚少。Toll样受体2（TLR2）和Toll样受体4（TLR4）参与哮喘和2型糖尿病（T2DM）的进展。这些受体分别参与对革兰氏阳性菌和革兰氏阴性菌的炎症反应，因此它们表达的变化可能影响患者发生菌血症的易感性。本研究的目的是分析TLR2和TLR4在BA、T2DM以及BA + T2DM患者外周血细胞上的表达及功能活性。通过流式细胞术分析TLR2和TLR4的表达。全血样本与大肠杆菌的脂多糖（LPS）和金黄色葡萄球菌的脂磷壁酸（LTA）孵育。采用酶联免疫吸附测定法（ELISA）测定细胞因子和可溶性血液蛋白的浓度。与健康供体和BA患者相比，合并症患者单核细胞和中性粒细胞上TLR2的表达在统计学上显著增加。我们发现患者血液单核细胞表面TLR4的表达高于供体。用LPS或LTA激活患者和供体的血细胞会导致“快速”促炎细胞因子（TNF-α、IL-6）表达增加。在BA患者中，对内毒素反应产生的TNF-α平均产量比其他研究组高两倍。T2DM和BA + T2DM患者血细胞的反应无显著差异。合并症患者血细胞上TLR2和TLR4的表达及功能活性与仅T2DM患者相似。在BA患者中，观察到对LPS和LTA反应时促炎细胞因子TNF-α的合成增加最为显著，这可能导致对菌血症的反应不足。
