Hepatoprotective and anti-inflammatory cytokines in alcoholic liver disease.
Hepatoprotective and anti-inflammatory cytokines in alcoholic liver disease.
复制标题
DOI：
10.1111/j.1440-1746.2011.07003.x
复制
发表时间：
2012-03
影响因子：
4.1
通讯作者：
Gao B
中科院分区：
文献类型：
--
作者：
Gao B
多种因素（如脂多糖和补体）激活固有免疫在引发和促进酒精性肝损伤中起重要作用，其通过刺激库普弗细胞诱导氧化应激并产生促炎细胞因子（如肿瘤坏死因子[TNF]-α），从而导致肝细胞损伤。越来越多的证据表明，在酒精性肝损伤过程中，固有免疫的激活还刺激库普弗细胞产生肝脏保护细胞因子白细胞介素 - 6（IL - 6）和抗炎细胞因子IL - 10。IL - 6通过激活信号转导和转录激活因子3（STAT3）以及随后在肝细胞中诱导多种肝脏保护基因来防止酒精性肝损伤。IL - 10通过激活库普弗细胞/巨噬细胞中的STAT3以及随后抑制肝脏炎症来抑制酒精性肝脏炎症。近期研究表明，IL - 10在控制乙醇诱导的脂肪变性和肝损伤方面可能具有双重作用，它可通过抑制促炎细胞因子TNF - α从而减轻酒精性肝损伤，或者通过抑制肝脏保护细胞因子IL - 6从而加重酒精性肝损伤。IL - 22是另一种重要的肝脏保护细胞因子，它通过与肝细胞表面由IL - 10R2和IL - 22R受体链组成的复合物结合来防止急性和慢性酒精性肝损伤。最后，由于IL - 22具有抗氧化、抗凋亡、抗脂肪变性、增殖和抗菌作用，以及潜在的副作用少的额外优势，IL - 22治疗是治疗严重酒精性肝病的一种潜在治疗选择。
The activation of innate immunity by various factors (e.g., lipopolysaccharide and complements) plays an important role in initiating and promoting alcoholic liver injury via the stimulation of Kupffer cells to induce oxidative stress and to produce pro-inflammatory cytokines (e.g., tumor necrosis factor [TNF]-α) that cause hepatocellular damage. Accumulating evidence suggests that the activation of innate immunity also stimulates Kupffer cells to produce the hepatoprotective cytokine interleukin-6 (IL-6) and the anti-inflammatory cytokine IL-10 during alcoholic liver injury. IL-6 protects against alcoholic liver injury via the activation of signal transducer and activator of transcription 3 (STAT3) and the subsequent induction of a variety of hepatoprotective genes in hepatocytes. IL-10 inhibits alcoholic liver inflammation via the activation of STAT3 in Kupffer cells/macrophages and the subsequent inhibition of liver inflammation. Recent studies have suggested that IL-10 may play a dual role in controlling ethanol-induced steatosis and liver injury via the inhibition of the pro-inflammatory cytokine TNF-α, thereby ameliorating alcoholic liver injury, or via the inhibition of the hepatoprotective cytokine IL-6, thereby potentiating alcoholic liver injury. IL-22 is another important hepatoprotective cytokine that protects against acute and chronic alcoholic liver injury by binding to a complex composed of IL-10R2 and IL-22R receptor chains on the surfaces of hepatocytes. Finally, IL-22 treatment is a potential therapeutic option for treating severe forms of alcoholic liver disease because of its antioxidant, antiapoptotic, antisteatotic, proliferative, and antimicrobial effects, as well as the potential added benefit of few side effects.
登录
查看更多内容
DOI：
10.1002/hep.23009
发表时间：
2009-08
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Rao R
通讯作者：
Rao R
DOI：
10.1002/hep.24517
发表时间：
2011-09-02
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Miller AM;Wang H;Bertola A;Park O;Horiguchi N;Ki SH;Yin S;Lafdil F;Gao B
通讯作者：
Gao B
影响因子：
13.5
作者：
Hong, F;Radaeva, S;Gao, B
通讯作者：
Gao, B
影响因子：
13.5
作者：
Mandal, Palash;Park, Pil-Hoon;McMullen, Megan R.;Pratt, Brian T.;Nagy, Laura E.
通讯作者：
Nagy, Laura E.
影响因子：
8
作者：
Hong, F;Kim, WH;Gao, B
通讯作者：
Gao, B