Fernández-Celemín Laura, Pasko Nevi, Blomart Valerie, Thissen Jean-Paul
Unité de Diabétologie et Nutrition, Université catholique de Louvain, B-1200 Brussels, Belgium.
Am J Physiol Endocrinol Metab. 2002 Dec;283(6):E1279-90. doi: 10.1152/ajpendo.00054.2002. Epub 2002 Jul 2.
The role of TNF-alpha in muscle catabolism is well established, but little is known about the mechanisms of its catabolic action. One possibility could be that TNF-alpha impairs the production of local growth factors like IGF-I. The aim of this study was to investigate whether TNF-alpha can directly inhibit IGF-I gene and protein expression in muscle. First, we investigated whether the acute inflammation induced by endotoxin injection changes IGF-I and TNF-alpha mRNA in rat tibialis anterior muscle. Endotoxin rapidly increased TNF-alpha mRNA (7-fold at 1 h, P < 0.001) and later decreased IGF-I mRNA (-73% at 12 h, P < 0.001). Furthermore, in a model of C2C12 myotubes, TNF-alpha strongly inhibited IGF-I mRNA and protein (-73 and -47% after 72 h, P < 0.001 and P < 0.01, respectively). Other proinflammatory cytokines failed to inhibit IGF-I mRNA. The effect of TNF-alpha on IGF-I mRNA was not mediated by nitric oxide, and the activation of NF-kappaB was insufficient to inhibit IGF-I expression. Taken together, our data suggest that TNF-alpha induced in muscle after LPS injection can locally inhibit IGF-I expression. The inhibition of muscle IGF-I production could contribute to the catabolic effect of TNF-alpha.
肿瘤坏死因子-α（TNF-α）在肌肉分解代谢中的作用已得到充分证实，但其分解代谢作用的机制却鲜为人知。一种可能性是TNF-α会损害胰岛素样生长因子-I（IGF-I）等局部生长因子的产生。本研究的目的是调查TNF-α是否能直接抑制肌肉中IGF-I基因和蛋白的表达。首先，我们研究了内毒素注射诱导的急性炎症是否会改变大鼠胫前肌中IGF-I和TNF-α的mRNA水平。内毒素迅速增加了TNF-α的mRNA（1小时时增加7倍，P<0.001），随后降低了IGF-I的mRNA（12小时时降低73%，P<0.001）。此外，在C2C12肌管模型中，TNF-α强烈抑制IGF-I的mRNA和蛋白（72小时后分别降低73%和47%，P<0.001和P<0.01）。其他促炎细胞因子未能抑制IGF-I的mRNA。TNF-α对IGF-I mRNA的作用不是由一氧化氮介导的，核因子-κB（NF-κB）的激活也不足以抑制IGF-I的表达。综上所述，我们的数据表明，脂多糖（LPS）注射后肌肉中诱导产生的TNF-α可局部抑制IGF-I的表达。肌肉中IGF-I生成的抑制可能有助于TNF-α的分解代谢作用。
