Figueras Maite, Busquets Sílvia, Carbó Neus, Barreiro Esther, Almendro Vanessa, Argilés Josep M, López-Soriano Francisco J
Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Barcelona, Spain.
FEBS Lett. 2004 Jul 2;569(1-3):201-6. doi: 10.1016/j.febslet.2004.05.066.
Administration of interleukin-15 (IL-15) to rats bearing the Yoshida AH-130 ascites hepatoma (a tumour that induces an important cachectic response) resulted in a significant reduction of muscle wasting, both measured as muscle weight and as protein content of different types of skeletal muscle. In addition, the administration of the cytokine completely reversed the increased DNA fragmentation observed in skeletal muscle of tumour-bearing animals. Concerning the mechanism(s) involved in the anti-apoptotic effects of IL-15 on skeletal muscle, the administration of the cytokine resulted in a considerable decrease in both R1 (43%) and R2 (64%) TNF-alpha receptors (TNFRs), and therefore it may be suggested that IL-15 decreases apoptosis by affecting TNF-alpha signalling. Formation of NO could be the signalling event associated with the activation of apoptosis in muscle of tumour-bearing rats; indeed, administration of IL-15 decreased the inducible nitric oxide synthase protein levels by 73%, suggesting that NO formation and muscle apoptosis during tumour growth are related. In conclusion, IL-15 seems to be able to reduce/suppress protein loss and apoptosis related to muscle wasting during cancer cachexia in experimental animals.
给携带吉田AH - 130腹水肝癌（一种引发显著恶病质反应的肿瘤）的大鼠注射白细胞介素 - 15（IL - 15），结果显示肌肉萎缩显著减轻，这一减轻通过肌肉重量以及不同类型骨骼肌的蛋白质含量来衡量。此外，细胞因子的注射完全逆转了在荷瘤动物骨骼肌中观察到的DNA片段化增加现象。关于IL - 15对骨骼肌抗凋亡作用所涉及的机制，细胞因子的注射导致R1（43%）和R2（64%）肿瘤坏死因子 - α受体（TNFRs）显著减少，因此可以推测IL - 15通过影响肿瘤坏死因子 - α信号传导来减少细胞凋亡。一氧化氮（NO）的形成可能是与荷瘤大鼠肌肉中细胞凋亡激活相关的信号事件；实际上，IL - 15的注射使诱导型一氧化氮合酶蛋白水平降低了73%，这表明肿瘤生长过程中NO的形成与肌肉细胞凋亡有关。总之，在实验动物中，IL - 15似乎能够减少/抑制与癌症恶病质期间肌肉萎缩相关的蛋白质损失和细胞凋亡。
