Palmitate and insulin synergistically induce IL-6 expression in human monocytes.
Palmitate and insulin synergistically induce IL-6 expression in human monocytes.
复制标题
DOI：
10.1186/1475-2840-9-73
复制
发表时间：
2010-11-05
影响因子：
9.3
通讯作者：
Fowlkes JL
中科院分区：
文献类型：
--
作者：
Bunn RC;Cockrell GE;Ou Y;Thrailkill KM;Lumpkin CK Jr;Fowlkes JL
胰岛素抵抗与促炎状态相关，促炎状态可促进2型糖尿病（T2DM）和动脉粥样硬化等并发症的发生。在胰岛素抵抗中，引发和传播促炎细胞因子的代谢刺激和促炎细胞因子的细胞起源尚未完全阐明。在肥胖、胰岛素抵抗的人群中，循环促炎单核细胞表现出炎症增强的迹象，因此是促炎细胞因子产生的潜在来源。在胰岛素抵抗的受试者中，可能刺激单核细胞炎症的特定循环代谢因子的特征尚不清楚。我们研究了饱和非酯化脂肪酸（NEFA）和胰岛素（随着胰岛素抵抗的发展而增加）是否能触发人单核细胞中白细胞介素(IL)-6和肿瘤坏死因子(TNF)-α的产生。采用实时荧光定量PCR （qRT-PCR）和Luminex生物测定法检测促炎细胞因子IL-6和TNF-α的信使RNA和蛋白水平。采用学生t检验，p < 0.05为显著性水平。在THP-1单核细胞诱导IL-6和TNF-α时，棕榈酸酯与辅酶A （CoA）的酯化反应是必需的，而β-氧化和神经酰胺的生物合成则不需要。与单独用棕榈酸酯孵育的单核细胞相比，胰岛素和棕榈酸酯共同孵育的单核细胞产生更多的IL-6 mRNA和蛋白，以及更多的TNF-α蛋白。单核细胞单独与胰岛素孵育不影响IL-6或TNF-α的产生。PI3K-Akt和MEK/ERK信号通路都是棕榈酸盐诱导细胞因子的重要信号通路。MEK/ERK信号是棕榈酸盐和胰岛素协同诱导IL-6的必要条件。高水平的饱和NEFA，如棕榈酸盐，当与高胰岛素血症结合时，可能激活人单核细胞产生促炎细胞因子，并支持亚急性、慢性炎症状态的发展和繁殖，这是胰岛素抵抗的特征。β-氧化和神经酰胺生物合成途径抑制剂的研究结果表明，通过甘油脂生物合成途径增加的脂肪酸通量可能参与促进单核细胞促炎细胞因子的产生。
Insulin resistance is associated with a proinflammatory state that promotes the development of complications such as type 2 diabetes mellitus (T2DM) and atherosclerosis. The metabolic stimuli that initiate and propagate proinflammatory cytokine production and the cellular origin of proinflammatory cytokines in insulin resistance have not been fully elucidated. Circulating proinflammatory monocytes show signs of enhanced inflammation in obese, insulin resistant subjects and are thus a potential source of proinflammatory cytokine production. The specific, circulating metabolic factors that might stimulate monocyte inflammation in insulin resistant subjects are poorly characterized. We have examined whether saturated nonesterified fatty acids (NEFA) and insulin, which increase in concentration with developing insulin resistance, can trigger the production of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in human monocytes. Messenger RNA and protein levels of the proinflammatory cytokines IL-6 and TNF-α were measured by quantitative real-time PCR (qRT-PCR) and Luminex bioassays. Student's t-test was used with a significance level of p < 0.05 to determine significance between treatment groups. Esterification of palmitate with coenzyme A (CoA) was necessary, while β-oxidation and ceramide biosynthesis were not required, for the induction of IL-6 and TNF-α in THP-1 monocytes. Monocytes incubated with insulin and palmitate together produced more IL-6 mRNA and protein, and more TNF-α protein, compared to monocytes incubated with palmitate alone. Incubation of monocytes with insulin alone did not affect the production of IL-6 or TNF-α. Both PI3K-Akt and MEK/ERK signalling pathways are important for cytokine induction by palmitate. MEK/ERK signalling is necessary for synergistic induction of IL-6 by palmitate and insulin. High levels of saturated NEFA, such as palmitate, when combined with hyperinsulinemia, may activate human monocytes to produce proinflammatory cytokines and support the development and propagation of the subacute, chronic inflammatory state that is characteristic of insulin resistance. Results with inhibitors of β-oxidation and ceramide biosynthesis pathways suggest that increased fatty acid flux through the glycerolipid biosynthesis pathway may be involved in promoting proinflammatory cytokine production in monocytes.
登录
查看更多内容
影响因子：
15.9
作者：
Cusi, K;Maezono, K;Mandarino, LJ
通讯作者：
Mandarino, LJ
影响因子：
4.2
作者：
Ajuwon, KM;Spurlock, ME
通讯作者：
Spurlock, ME
影响因子：
29
作者：
Bouhlel, M. Amine;Derudas, Bruno;Chinetti-Gbaguidi, Giulia
通讯作者：
Chinetti-Gbaguidi, Giulia
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：
29
作者：
Baumgartl, J;Baudler, S;Brüning, JC
通讯作者：
Brüning, JC