Dissociation between liver inflammation and hepatocellular damage induced by carbon tetrachloride in myeloid cell-specific signal transducer and activator of transcription 3 gene knockout mice.
Dissociation between liver inflammation and hepatocellular damage induced by carbon tetrachloride in myeloid cell-specific signal transducer and activator of transcription 3 gene knockout mice.
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DOI：
10.1002/hep.23532
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发表时间：
2010-05
期刊：
影响因子：
13.5
通讯作者：
Gao, Bin
中科院分区：
文献类型：
--
作者：
Horiguchi, Norio;Lafdil, Fouad;Miller, Andrew M.;Park, Ogyi;Wang, Hua;Rajesh, Mohanraj;Mukhopadhyay, Partha;Fu, Xin Yuan;Pacher, Pal;Gao, Bin
肝损伤与炎症有关，一般认为炎症会加速肝脏疾病的进展；然而，临床数据显示，在一些患者中，炎症并不总是与肝细胞损伤相关。利用实验动物模型研究这些事件背后的细胞机制，我们发现炎症可以减轻骨髓特异性信号换能器和转录激活因子3 （STAT3）敲除小鼠中四氯化碳（CCl4）诱导的肝坏死。作为一种重要的抗炎信号，注射CCl4后，骨髓细胞中STAT3的条件性缺失导致肝脏炎症明显增强。然而，这些作用也伴随着肝坏死减少，与血清IL-6和肝脏STAT3激活升高相关。骨髓特异性STAT3敲除小鼠肝细胞中STAT3的额外缺失恢复了肝坏死，但减少了肝脏炎症。结论：炎症介导的STAT3激活减轻了髓细胞特异性STAT3敲除小鼠CCl4诱导的肝细胞损伤，提示炎症与激活肝STAT3的肝保护细胞因子优势相关，可能减轻而不是加速慢性肝病患者的肝细胞损伤。
Liver injury is associated with inflammation, which is generally believed to accelerate the progression of liver diseases; however, clinical data show that inflammation does not always correlate with hepatocelluar damage in some patients. Investigating the cellular mechanisms underlying these events using an experimental animal model, we show that inflammation may attenuate liver necrosis induced by carbon tetrachloride (CCl4) in myeloid-specific signal transducer and activator of transcription 3 (STAT3) knockout mice. As an important anti-inflammatory signal, conditional deletion of STAT3 in myeloid cells results in markedly enhanced liver inflammation after CCl4 injection. However, these effects are also accompanied by reduced liver necrosis, correlating with elevated serum IL-6 and hepatic STAT3 activation. An additional deletion of STAT3 in hepatocytes in myeloid-specific STAT3 knockout mice restored hepatic necrosis, but decreased liver inflammation. Conclusions: Inflammation-mediated STAT3 activation attenuates hepatocellular injury induced by CCl4 in myeloid-specific STAT3 knockout mice, suggesting that inflammation associated with a predominance of hepatoprotective cytokines that activate hepatic STAT3 may reduce rather than accelerate hepatocellular damage in patients with chronic liver diseases.
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影响因子：
13.5
作者：
Fracanzani, Anna Ludovica;Valenti, Luca;Fargion, Silvia
通讯作者：
Fargion, Silvia
影响因子：
13.5
作者：
Sakamori, Ryotaro;Takehara, Tetsuo;Hayashi, Norio
通讯作者：
Hayashi, Norio
影响因子：
13.5
作者：
Blindenbacher, A;Wang, XY;Heim, MH
通讯作者：
Heim, MH
DOI：
10.1111/j.1749-6632.2009.03704.x
发表时间：
2009-01-01
期刊：
STEROID ENZYMES AND CANCER
影响因子：
--
作者：
Berasain, C.;Castillo, J.;Avila, M. A.
通讯作者：
Avila, M. A.
影响因子：
13.5
作者：
Louis, H;Van Laethem, JL;Devière, J
通讯作者：
Devière, J