Elevated interleukin-6 during ethanol consumption acts as a potential endogenous protective cytokine against ethanol-induced apoptosis in the liver:: involvement of induction of Bcl-2 and Bcl-XL proteins
Elevated interleukin-6 during ethanol consumption acts as a potential endogenous protective cytokine against ethanol-induced apoptosis in the liver:: involvement of induction of Bcl-2 and Bcl-XL proteins
复制标题
DOI：
10.1038/sj.onc.1205016
复制
发表时间：
2002-01-03
期刊：
影响因子：
8
通讯作者：
Gao, B
中科院分区：
文献类型：
--
作者：
Hong, F;Kim, WH;Gao, B
血清白细胞介素 - 6（IL - 6）水平升高总是与酒精性肝病（ALD）相关，但其升高的意义尚不清楚。在此我们表明，长期摄入乙醇会在IL - 6（-/-）小鼠肝脏中诱导显著的细胞凋亡，但在IL - 6（+/+）小鼠中不会。IL - 6（-/-）肝细胞对乙醇和肿瘤坏死因子α（TNF - α）诱导的凋亡杀伤更敏感，而IL - 6可纠正这种情况。在人类ALD患者肝脏以及长期摄入乙醇的IL - 6（+/+）小鼠肝脏中，抗凋亡蛋白（如Bcl - 2和Bcl - X - L）和促凋亡蛋白（如Bax）的表达均显著升高。相反，在长期摄入乙醇的IL - 6（-/-）小鼠肝脏中未观察到Bcl - 2和Bcl - X - L的诱导，而Bax蛋白的表达仍然升高。注射IL - 6可显著诱导肝脏中Bcl - 2和Bcl - XL的表达，但不诱导Bax的表达。最后，高浓度乙醇抑制IL - 6激活的抗凋亡信号，但增加IL - 6的浓度能够克服这种抑制作用。这些发现表明，ALD中血清IL - 6水平升高可能克服乙醇对IL - 6介导的抗凋亡信号的抑制作用，并通过诱导Bcl - 2和Bcl - X - L防止酒精诱导的肝细胞凋亡。
Elevation of serum interleukin-6 (IL-6) levels is always associated with alcoholic liver disease (ALD), but the significance of such elevation is not clear. Here we show that chronic ethanol consumption induces significant apoptosis in the liver of IL-6 (-/-) mice but not IL-6 (+/+) mice. IL-6 (-/-) hepatocytes are more susceptible to ethanol- and tumor necrosis factor alpha- (TNF alpha-) induced apoptotic killing, which can be corrected by IL-6. Expression of both anti-apoptotic (such as Bcl-2 and Bcl-X-L) and proapoptotic (such as Bax) proteins is markedly elevated in the liver of human ALD and chronically ethanol-fed IL-6 (+/+) mice. On the contrary, induction of Bcl-2 and Bcl-X-L is not observed in the liver of chronically ethanol-fed IL-6 (-/-) mice, whereas expression of Bax protein remains elevated. Injection of IL-6 markedly induces expression of Bcl-2 and Bcl-XL but not Bax in the liver. Finally, high concentrations of ethanol inhibit IL-6-activated anti-apoptotic signal, but increasing the concentrations of IL-6 is able to overcome such inhibitory effect. These findings suggest that elevated serum IL-6 levels in ALD may overcome the inhibitory effect of ethanol on IL-6-mediated anti-apoptotic signals and prevent alcohol-induced hepatic apoptosis by induction of Bcl-2 and Bcl-X-L.