Kupffer cells in non-alcoholic fatty liver disease: the emerging view.
Kupffer cells in non-alcoholic fatty liver disease: the emerging view.
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DOI：
10.1016/j.jhep.2009.03.008
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发表时间：
2009-07
影响因子：
25.7
通讯作者：
Baffy G
中科院分区：
文献类型：
--
作者：
Baffy G
非酒精性脂肪性肝病（NAFLD）已成为我们这个时代最常见的肝脏疾病。单纯性脂肪变性是NAFLD的一种看似无害的表现，可能会发展为脂肪性肝炎和肝硬化，但这一过程尚不清楚。由于NAFLD与肥胖和胰岛素抵抗相关，因此将脂质代谢与炎症联系起来的机制为发病机制提供了见解。脂肪组织和肝脏的肥胖相关病理学之间的一个重要平行关系涉及巨噬细胞的新兴作用，并且越来越多的证据表明枯否细胞对NAFLD的进展有重要贡献。Toll样受体，特别是TLR4，代表了与枯否细胞活化相关的危险识别的主要渠道，并且该过程可能在NAFLD的多个步骤中受到干扰。脂肪变性可能干扰窦状微循环和肝细胞清除微生物和宿主来源的危险信号，增强枯否细胞的反应性。NAFLD中脂质稳态的改变可能不利地影响TLR4受体复合物的组装和分选，干扰信号传导通量的再分布，促进放大环，并损害包括库普弗细胞的交替激活在内的负调节。脂肪因子分泌和活性氧簇产生的改变进一步促进了这些事件。针对这些相互作用的特异性靶向可能为NAFLD的治疗提供更有效的策略。
Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disorder of our times. Simple steatosis, a seemingly innocent manifestation of NAFLD, may progress into steatohepatitis and cirrhosis, but this process is not well understood. Since NAFLD is associated with obesity and insulin resistance, mechanisms that link lipid metabolism to inflammation offer insights into the pathogenesis. An important parallel between obesity-related pathology of adipose tissue and liver pertains to the emerging role of macrophages and evidence is growing that Kupffer cells critically contribute to progression of NAFLD. Toll-like receptors, in particular TLR4, represent a major conduit for danger recognition linked to Kupffer cell activation and this process may be perturbed at multiple steps in NAFLD. Steatosis may interfere with sinusoid microcirculation and hepatocellular clearance of microbial and host-derived danger signals, enhancing responsiveness of Kupffer cells. Altered lipid homeostasis in NAFLD may unfavourably affect TLR4 receptor complex assembly and sorting, interfere with signalling flux redistribution, promote amplification loops, and impair negative regulation including alternative activation of Kupffer cells. These events are further promoted by altered adipokine secretion and reactive oxygen species production. Specific targeting of these interactions may provide more effective strategies in the treatment of NAFLD.
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影响因子：
4.1
作者：
Emre, Yalin;Hurtaud, Corinne;Cassard-Doulcier, Anne-Marie
通讯作者：
Cassard-Doulcier, Anne-Marie
影响因子：
25.7
作者：
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通讯作者：
Ramadori, G
影响因子：
15.9
作者：
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通讯作者：
van der Westhuyzen, Deneys R.
影响因子：
4.1
作者：
BOVERIS, A;CHANCE, B
通讯作者：
CHANCE, B
影响因子：
5.8
作者：
Andrés, D;Sánchez-Reus, I;Cascales, M
通讯作者：
Cascales, M