Increased adipose tissue expression of TLR8 in obese individuals with or without type-2 diabetes: significance in metabolic inflammation.
Increased adipose tissue expression of TLR8 in obese individuals with or without type-2 diabetes: significance in metabolic inflammation.
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DOI：
10.1186/s12950-016-0147-y
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Sindhu S
中科院分区：
文献类型：
--
作者：
Ahmad R;Kochumon S;Thomas R;Atizado V;Sindhu S
先天免疫Toll样受体（TLR）2/4是肥胖和2型糖尿病（T2 D）中称为代谢性炎症的慢性低度炎症的重要参与者。虽然与代谢性炎症相关的TLR 2/4表达变化是已知的，但由所有主要巨噬细胞亚群表达的内吞TLR 8的脂肪组织表达仍不清楚。因此，我们确定了TLR 8 mRNA/蛋白质表达的脂肪组织样本瘦，超重，肥胖的个人或没有T2 D。从49名非糖尿病患者（23名肥胖、17名超重和9名瘦型）和45名T2 D患者（32名肥胖、10名超重和3名瘦型）中采集皮下脂肪活检样本。使用实时RT-PCR测定TLR 8基因表达，并通过免疫组织化学和共聚焦显微镜评估TLR 8蛋白表达。将TLR 8表达的变化与巨噬细胞标志物、促炎细胞因子/趋化因子和表面TLRs/衔接蛋白的变化进行比较。采用t检验/Mann-Whitney U检验、Pearson相关分析和多元回归分析。结果显示，肥胖非糖尿病/T2 D患者TLR 8基因表达水平显著高于瘦型患者，且与非糖尿病人群的体重指数（BMI）和体脂百分比相关（P < 0.05）。正如预期的那样，非糖尿病/T2 D肥胖个体中的TLR 8脂肪组织蛋白表达也高于超重/瘦的对应者。在非糖尿病/T2 D个体中，TLR 8基因表达与CD 68、CD 11 c、CD 86和CD 163巨噬细胞标志物的表达相关（P < 0.05）。此外，在这些个体中，TLR 8基因表达与TNF-α、IL-18和IL-8的脂肪组织表达以及全身CRP水平（在非糖尿病患者中）正相关（P < 0.05）。TLR 8的表达与TLR 4/TLR 2和MyD 88在脂肪组织中的表达相关。肥胖/T2 D中TLR 8的脂肪组织表达升高与炎症特征一致，因此可能代表代谢性炎症的免疫标志物。本文的在线版本（doi：10.1186/s12950-016-0147-y）包含补充材料，可供授权用户使用。
The innate immune Toll-like receptors (TLRs) 2/4 are important players in chronic low-grade inflammation called metabolic inflammation in obesity and type-2 diabetes (T2D). While TLR2/4 expression changes associated with metabolic inflammation are known, the adipose tissue expression of endocytic TLR8, which is expressed by all major macrophage subsets, remain unclear. We, therefore, determined the TLR8 mRNA/protein expression in the adipose tissue samples from lean, overweight, and obese individuals with or without T2D. Subcutaneous fat biopsy samples were collected from 49 non-diabetic (23 obese, 17 overweight, and nine lean) and 45 T2D (32 obese, ten overweight, and three lean) individuals. TLR8 gene expression was determined using real-time RT-PCR and TLR8 protein expression was assessed by both immunohistochemistry and confocal microscopy. The changes in TLR8 expression were compared with those of macrophage markers, proinflammatory cytokines/chemokines, and surface TLRs/adapter proteins. The data were analyzed using t-test/Mann-Whitney U-test, Pearson’s correlation, and multiple regression test. The data show that in obese non-diabetic/T2D individuals, TLR8 gene expression was significantly upregulated as compared with lean individuals which correlated with body mass index (BMI) and body fat percentage in non-diabetic population (P < 0.05). As expected, TLR8 adipose tissue protein expression in non-diabetic/T2D obese individuals was also higher than that of overweight/lean counterparts. In non-diabetic/T2D individuals, TLR8 gene expression associated (P < 0.05) with the expression of CD68, CD11c, CD86, and CD163 macrophage markers. Also, in these individuals, TLR8 gene expression correlated positively (P < 0.05) with adipose tissue expression of TNF-α, IL-18, and IL-8 as well as with systemic CRP levels (in non-diabetics). TLR8 expression was also associated with TLR4/TLR2 and MyD88 expression in the adipose tissue. The elevated adipose tissue expression of TLR8 in obesity/T2D has consensus with inflammatory signatures and may thus represent an immune marker of metabolic inflammation. The online version of this article (doi:10.1186/s12950-016-0147-y) contains supplementary material, which is available to authorized users.
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DOI：
10.1186/1476-9255-9-48
发表时间：
2012-11-28
期刊：
Journal of inflammation (London, England)
影响因子：
--
作者：
Ahmad R;Al-Mass A;Atizado V;Al-Hubail A;Al-Ghimlas F;Al-Arouj M;Bennakhi A;Dermime S;Behbehani K
通讯作者：
Behbehani K
影响因子：
7.7
作者：
Lumeng, Carey N.;DeYoung, Stephanie M.;Saltiel, Alan R.
通讯作者：
Saltiel, Alan R.
影响因子：
3.1
作者：
Cario, E;Podolsky, DK
通讯作者：
Podolsky, DK
影响因子：
4.9
作者：
Kim, C-S;Park, H-S;Yu, R.
通讯作者：
Yu, R.
影响因子：
8.2
作者：
Lee, C. C.;Adler, A. I.;Wareham, N. J.
通讯作者：
Wareham, N. J.