Changes in the Adipose Tissue Expression of CD86 Costimulatory Ligand and CD163 Scavenger Receptor in Obesity and Type-2 Diabetes: Implication for Metabolic Disease

Sardar Sindhu, Reeby Thomas, Shihab Kochumon, Eman Alshawaf, Amal Hasan, Munera Alghanim, Kazem Behbehanil, R. Ahmad
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引用次数: 9

Abstract

Background: The CD86 costimulatory ligand and CD163 scavenger receptor are expressed on monocytes/macrophages. However, modulations in the expression of these immune regulatory receptors in metabolic disease remain unclear. We, therefore, compared the adipose tissue expression of CD86/CD163 and signature inflammatory cytokines/chemokines in non-diabetic and diabetic individuals. Methods: Subcutaneous adipose tissue biopsies were collected from 57 non-diabetics and 46 diabetics classified based on body mass index as obese, overweight and lean and the expression of CD86/CD163 was assessed by quantitative RT-PCR, immunohistochemistry/ confocal microscopy. Results: The data show that CD86 and CD163 gene expression was elevated in non-diabetic obese individuals as compared with their lean counterparts (P [CD86] = 0.0035; P [CD163] = 0.0028). As expected, CD86 and CD163 protein expression was also found to be elevated in the adipose tissue samples of obese individuals. The CD86 gene expression in non-diabetic and diabetic individuals correlated positively (P<0.05) with that of TNF-α (r [non-diabetic] = 0.26; r [diabetic] = 0.49), IL-18 (r [non-diabetic] = 0.67; r [diabetic] = 0.63), and IL-8 (r [non-diabetic] = 0.38; r [diabetic] = 0.33). The CD86 gene expression correlated significantly with that of IL-23 and IP-10 in non-diabetic individuals. The CD86 gene expression also correlated with glycated hemoglobin (r [diabetic] = 0.38; P = 0.007). In parallel, CD163 gene expression also correlated positively (P<0.05) with TNF-α (r [non-diabetic] = 0.35; r [diabetic] = 0.38), IL-18 (r [non-diabetic] = 0.72; r [diabetic] = 0.71), IL-23 (r [non-diabetic] = 0.28), and IL-8 (r [non-diabetic] = 0.58; r [diabetic] = 0.35). The adipose tissue expression of IL-18 independently predicted the expression of CD86 and CD163 both in non-diabetic and diabetic individuals. Conclusion: The adipose tissue expression of CD86 and CD163 is elevated in obesity and T2D which has consensus with inflammatory signatures and represents novel immune markers for metabolic inflammation.
肥胖和2型糖尿病患者脂肪组织中CD86共刺激配体和CD163清道夫受体表达的变化:对代谢性疾病的影响
背景:CD86共刺激配体和CD163清道夫受体在单核细胞/巨噬细胞上表达。然而,这些免疫调节受体在代谢性疾病中的表达调控仍不清楚。因此,我们比较了非糖尿病和糖尿病个体中CD86/CD163和标志性炎症细胞因子/趋化因子的脂肪组织表达。方法:选取57例非糖尿病患者和46例按体重指数分为肥胖、超重和瘦弱的糖尿病患者皮下脂肪组织活检,采用定量RT-PCR、免疫组织化学/共聚焦显微镜检测CD86/CD163的表达。结果:数据显示,CD86和CD163基因在非糖尿病性肥胖个体中表达水平高于瘦人(P [CD86] = 0.0035;P [cd163] = 0.0028)。正如预期的那样,CD86和CD163蛋白表达在肥胖个体的脂肪组织样本中也被发现升高。非糖尿病和糖尿病患者CD86基因表达与TNF-α呈正相关(P<0.05) (r[非糖尿病]= 0.26;r[糖尿病]= 0.49),IL-18 (r[非糖尿病]= 0.67;r[糖尿病患者]= 0.63),IL-8 (r[非糖尿病患者]= 0.38;R[糖尿病]= 0.33)。非糖尿病患者CD86基因表达与IL-23、IP-10表达显著相关。CD86基因表达也与糖化血红蛋白相关(r [diabetes] = 0.38;P = 0.007)。CD163基因表达也与TNF-α呈正相关(P<0.05) (r[非糖尿病]= 0.35;r[糖尿病]= 0.38),IL-18 (r[非糖尿病]= 0.72;r[糖尿病]= 0.71)、IL-23 (r[非糖尿病]= 0.28)、IL-8 (r[非糖尿病]= 0.58;R[糖尿病]= 0.35)。在非糖尿病和糖尿病个体中,IL-18的脂肪组织表达独立预测CD86和CD163的表达。结论:脂肪组织中CD86和CD163的表达在肥胖和T2D中升高,这与炎症特征一致,是代谢性炎症的新免疫标志物。
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