Division of Molecular and Life Science, Department of Life Science, Pohang University of Science and Technology (POSTECH), San 31, Hyoja Dong, Pohang 790-784, Republic of Korea.
J Mol Endocrinol. 2010 Apr;44(4):225-36. doi: 10.1677/JME-09-0161. Epub 2010 Jan 20.
Interleukin 6 (IL6) is a pleiotropic cytokine that not only affects the immune system, but also plays an active role in many physiological events in various organs. Notably, 35% of systemic IL6 originates from adipose tissues under noninflammatory conditions. Here, we describe a previously unknown function of melanocortins in regulating Il6 gene expression and production in 3T3-L1 adipocytes through membrane receptors which are called melanocortin receptors (MCRs). Of the five MCRs that have been cloned, MC2R and MC5R are expressed during adipocyte differentiation. alpha-Melanocyte-stimulating hormone (alpha-MSH) or ACTH treatment of 3T3-L1 adipocytes induces Il6 gene expression and production in a time- and concentration-dependent manner via various signaling pathways including the protein kinase A, p38 mitogen-activated protein kinase, cJun N-terminal kinase, and IkappaB kinase pathways. Specific inhibition of MC2R and MC5R expression with short interfering Mc2r and Mc5r RNAs significantly attenuated the alpha-MSH-induced increase of intracellular cAMP and both the level of Il6 mRNA and secretion of IL6 in 3T3-L1 adipocytes. Finally, when injected into mouse tail vein, alpha-MSH dramatically increased the Il6 transcript levels in epididymal fat pads. These results suggest that alpha-MSH in addition to ACTH may function as a regulator of inflammation by regulating cytokine production.
白细胞介素 6（IL6）是一种多效细胞因子，不仅影响免疫系统，而且在各种器官的许多生理事件中发挥积极作用。值得注意的是，35%的系统性 IL6 来源于非炎症条件下的脂肪组织。在这里，我们描述了一种以前未知的黑素细胞激素功能，即通过称为黑素细胞受体（MCR）的膜受体调节 3T3-L1 脂肪细胞中 Il6 基因的表达和产生。在已经克隆的五个 MCR 中，MC2R 和 MC5R 在脂肪细胞分化过程中表达。α-促黑素细胞激素（α-MSH）或 ACTH 处理 3T3-L1 脂肪细胞通过包括蛋白激酶 A、p38 丝裂原激活蛋白激酶、cJun N 末端激酶和 IkappaB 激酶途径在内的各种信号通路，以时间和浓度依赖的方式诱导 Il6 基因的表达和产生。用短干扰 Mc2r 和 Mc5r RNA 特异性抑制 MC2R 和 MC5R 的表达，显著减弱了α-MSH 诱导的 3T3-L1 脂肪细胞内 cAMP 增加以及 Il6 mRNA 水平和 IL6 分泌的增加。最后，当注射到小鼠尾静脉时，α-MSH 可显著增加附睾脂肪垫中 Il6 的转录水平。这些结果表明，α-MSH 除了 ACTH 之外，还可以通过调节细胞因子的产生来调节炎症。
