Elevated expression of the toll like receptors 2 and 4 in obese individuals: its significance for obesity-induced inflammation.
Elevated expression of the toll like receptors 2 and 4 in obese individuals: its significance for obesity-induced inflammation.
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DOI：
10.1186/1476-9255-9-48
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发表时间：
2012-11-28
期刊：
影响因子：
--
通讯作者：
Behbehani K
中科院分区：
文献类型：
--
作者：
Ahmad R;Al-Mass A;Atizado V;Al-Hubail A;Al-Ghimlas F;Al-Arouj M;Bennakhi A;Dermime S;Behbehani K
PBMC 上 Toll 样受体 (TLR) 的表达谱对于促炎标志物的调节至关重要。 TLR 表达失衡可能导致多种类型的炎症性疾病。此外，肥胖个体中炎症活动的动态调节以及相关的外周血单核细胞（PBMC）产生的细胞因子受损仍然知之甚少。因此，我们确定了 TLR（TLR2 和 TLR4）及其接头蛋白（MyD88、IRAK1 和 TRAF6）在 PBMC/皮下脂肪组织 (AT) 中表达的扰动以及肥胖个体中炎症细胞因子的变化。通过RT-PCR测定TLR2、TLR4、IL-6、TNF-α和接头蛋白的mRNA表达水平。通过免疫组织化学测定 AT 中 TLR2、TLR4 和接头蛋白的表达。与瘦个体相比，肥胖和超重个体的 PBMC 和 AT 中 TLR2、TLR4 和 MyD88 的表达显着增加（P<0.05）。有趣的是，我们发现肥胖和超重的 2 型糖尿病患者中 TLR 的表达显着升高（P<0.05）。 TLR2、TLR4、MyD88 和 IRAK1 表达增加与体重指数 (BMI) 相关（TLR2：r = 0.91；TLR4：r = 0.88，P <0.0001；MyD88：r = 0.95，P < 0.0001；IRAK1 r = 0.78，P < 0.002)。 TLRs的表达还与空腹血糖（FBG）（TLR2：r = 0.61，P < 0.002；TLR4：r = 0.52，P < 0.01）和糖化血红蛋白（HbA1c）相关（TLR2：r = 0.44，P <0.03；TLR4：r = 0.48，P < 0.03）。与瘦受试者相比，肥胖受试者的 IL-6 和 TNF-α 转录水平显着升高。 PBMC 中 TLR 的表达与 TNF-α (TLR2: r = 0.92; TLR4: r = 0.92; P < 0.0001) 和 IL-6 (TLR2: r = 0.91, P < 0.0001; TLR4: r = 0.81；P < 0.001)。同样，接头蛋白与 TNF-α (MyD88：r = 0.9，P < 0.0001；IRAK1：r = 0.86；P < 0.0002) 和 IL-6 (MyD88：r = 0.91，P < 0.0001；P < 0.0002) 显着相关。伊拉克1：0.77；P < 0.002）。 TLR 和衔接蛋白在肥胖受试者的 PBMC 中过度表达，这与 TNF-α 和 IL-6 表达增加相关。这种关联可以解释肥胖和导致胰岛素抵抗的炎症之间潜在的病理生理学联系。
Expression profile of the toll like receptors (TLRs) on PBMCs is central to the regulation of proinflammatory markers. An imbalance in the TLRs expression may lead to several types of inflammatory disorders. Furthermore, the dynamic regulation of inflammatory activity and associated impaired production of cytokines by peripheral blood mononuclear cells (PBMCs) in obese individulas remain poorly understood. Therefore, we determined the perturbation in TLRs (TLR2 and TLR4), their adaptor proteins (MyD88, IRAK1 and TRAF6) expression in PBMCs/subcutaneous adipose tissue (AT) as well as inflammatory cytokines changes in obese individuals. mRNA expression levels of TLR2, TLR4, IL-6, TNF-α and adaptor proteins were determined by RT-PCR. TLR2, TLR4 and adaptor proteins expression in AT was determined by immunohistochemistry. Obese and overweight individuals showed significantly increased expression of TLR2, TLR4 and MyD88 in both PBMCs and AT as compared with lean individuals (P < 0.05). Interestingly, we found a remarkably higher expression of TLRs in obese and overweight individuals with type 2 diabetes (P < 0.05). Increased expression of TLR2, TLR4, MyD88 and IRAK1 correlated with body mass index (BMI) (TLR2: r = 0.91; TLR4: r = 0.88, P <0.0001; MyD88: r = 0.95, P < 0.0001; IRAK1 r = 0.78, P < 0.002). TLRs’ expression was also correlated with fasting blood glucose (FBG) (TLR2: r = 0.61, P < 0.002; TLR4: r = 0.52, P < 0.01) and glycated haemoglobin (HbA1c) ( TLR2: r = 0.44, P <0.03; TLR4: r = 0.48, P < 0.03). Transcript levels of IL-6 and TNF-α were highly elevated in obese subjects compared to lean subjects. There was a strong association of TLRs’ expression in PBMCs with TNF-α (TLR2: r = 0.92; TLR4: r = 0.92; P < 0.0001) and IL-6 (TLR2: r = 0.91, P < 0.0001; TLR4: r = 0.81; P < 0.001). Similarly adaptor proteins were significantly correlated with TNF-α (MyD88: r = 0.9, P < 0.0001; IRAK1: r = 0.86; P < 0.0002) and IL-6 (MyD88: r = 0.91, P < 0.0001; IRAK1: 0.77; P < 0.002). TLRs and adapter proteins were overexpressed in PBMCs from obese subjects, which correlated with increased expression of TNF-α and IL-6. This association may explain a potential pathophysiological link between obesity and inflammation leading to insulin resistance.
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影响因子：
7.7
作者：
Senn, JJ;Klover, PJ;Mooney, RA
通讯作者：
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作者：
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作者：
Kuo, L. -H.;Tsai, P. -J.;Tsai, Y. -S.
通讯作者：
Tsai, Y. -S.
影响因子：
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作者：
Ospelt, Caroline;Brentano, Fabia;Kyburz, Diego
通讯作者：
Kyburz, Diego