Interaction of osteopontin with IL-18 in obese individuals: implications for insulin resistance.
Interaction of osteopontin with IL-18 in obese individuals: implications for insulin resistance.
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DOI：
10.1371/journal.pone.0063944
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Behbehani K
中科院分区：
文献类型：
--
作者：
Ahmad R;Al-Mass A;Al-Ghawas D;Shareif N;Zghoul N;Melhem M;Hasan A;Al-Ghimlas F;Dermime S;Behbehani K
骨桥蛋白（OPN）和IL-18是已知的炎症介质，并且两者都参与与免疫性疾病相关的广泛的生物过程。由于OPN和IL-18之间的相互作用尚未在肥胖症中进行研究，因此我们研究了：（i）它们的水平是否在肥胖个体中同时升高;（ii）OPN是否与肥胖个体中的IL-18相关;以及（iii）它们的水平是否与空腹血糖（FBG）和BMI相关。PBMC和血浆样品分离自60个个体，包括瘦的以及超重和肥胖的个体。获得皮下脂肪组织样品。ELISA法检测骨桥蛋白（OPN）和白细胞介素18（IL-18）。采用真实的实时定量RT-PCR检测骨桥蛋白和IL-18 mRNA的表达。肥胖者的循环OPN水平显著高于瘦者（肥胖2865±101;瘦1681±116 pg/ml; P<0.0001）。肥胖个体中IL-18水平也较高（肥胖491±39，瘦301±26 pg/ml; P = 0.0009）。 与瘦型个体相比，肥胖个体的PBMC中OPN和IL-18表达同时上调（OPN：5.4倍; IL-18：8.9倍; P<0.05）。来自肥胖个体的脂肪组织具有OPN（7.3倍）和IL-18（9.6倍）的高表达。血浆OPN水平与FBG水平呈正相关（r = 0.32，P = 0.02）。 IL-18与FBG水平呈正相关（r = 0.406，P = 0.0042）。 逐步多元回归分析显示BMI与OPN和IL-18独立相关。有趣的是，OPN水平随着IL-18水平的增加而逐渐增加（r = 0.52，P = 0.0004）。 我们还研究了IL-18在PBMC分泌OPN中的调节作用。中和抗IL-18 R α mAb可减少OPN分泌。这些发现代表了第一个观察结果，即血浆、PBMC和脂肪组织OPN和IL-18同时增加，并且在超重/肥胖个体中彼此相关，这可能引发肥胖相关的胰岛素抵抗的发展。此外，这些结果提供了IL-18调节PBMC中OPN产生的直接证据。
Osteopontin (OPN) and IL-18 are known inflammatory mediators and both participate in a wide range of biological processes linked to immunological disorders. Since an interaction between OPN and IL-18 has not been studied in obesity, we investigated whether: (i) their levels were simultaneously elevated in obese individuals; (ii) OPN was associated with IL-18 in obese individuals and (iii) their levels associated with fasting blood glucose (FBG) and BMI. PBMCs and plasma samples were isolated from 60 individuals including lean as well as overweight and obese individuals. Subcutaneous adipose tissue samples were obtained. OPN and IL-18 were measured by ELISA. OPN and IL-18 mRNA expression was quantified by real time quantitative RT-PCR. Obese individuals exhibited significantly increased circulating OPN levels as compared with lean individuals (obese 2865±101; lean 1681±116 pg/ml; P<0.0001). IL-18 levels were also high in obese individuals (obese 491±39, lean 301±26 pg/ml; P = 0.0009). OPN and IL-18 expression were simultaneously up-regulated (OPN: 5.4-Fold; IL-18: 8.9-Fold; P<0.05) in PBMCs from obese individuals compared to lean group. Adipose tissue from obese individuals had high expression of OPN (7.3-Fold) and IL-18 (9.6-Fold). Plasma OPN levels correlated positively with FBG levels (r = 0.32, P = 0.02). Similarly, IL-18 correlated positively with FBG levels (r = 0.406, P = 0.0042). Stepwise multiple regression analysis showed an independent association of BMI with OPN and IL-18. Interestingly, OPN levels increased progressively with an increase in IL-18 levels (r = 0.52, P = 0.0004). We also examined the regulatory role of IL-18 in OPN secretion from PBMCs. Neutralizing anti-IL-18Rα mAb reduced OPN secretion. These findings represent the first observation that plasma, PBMC and adipose tissue OPN and IL-18 are simultaneously increased and correlate with each other in overweight/obese individuals which may trigger the development of obesity-associated insulin resistance. Moreover, these results provide the direct evidence that IL-18 regulates OPN production in PBMCs.
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影响因子：
5.8
作者：
Esposito, K;Pontillo, A;Giugliano, D
通讯作者：
Giugliano, D
肿瘤坏死因子-α的脂肪表达--在与肥胖相关的胰岛素抵抗中的直接作用
影响因子：
56.9
作者：
HOTAMISLIGIL, GS;SHARGILL, NS;SPIEGELMAN, BM
通讯作者：
SPIEGELMAN, BM
影响因子：
5.8
作者：
Bruun, Jens M.;Stallknecht, Bente;Richelsen, Bjorn
通讯作者：
Richelsen, Bjorn
影响因子：
6.9
作者：
Leick, Lotte;Lindegaard, Birgitte;Pilegaard, Henriette
通讯作者：
Pilegaard, Henriette
DOI：
10.1128/cdli.12.1.206-212.2005
发表时间：
2005-01-01
期刊：
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY
影响因子：
--
作者：
Kawamura, K;Iyonaga, K;Sasaki, Y
通讯作者：
Sasaki, Y