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首页> 外文期刊>Aging cell. >Age-related sensitivity to endotoxin-induced liver inflammation: Implication of inflammasome/IL-1 beta for steatohepatitis
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Age-related sensitivity to endotoxin-induced liver inflammation: Implication of inflammasome/IL-1 beta for steatohepatitis

机译：对内毒素诱导的肝脏炎症的年龄相关敏感性：炎性小体/ IL-1β对脂肪性肝炎的影响

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Aging is associated with increased vulnerability to inflammatory challenge. However, the effects of altered inflammatory response on the metabolic status of tissues or organs are not well documented. In this study, we present evidence demonstrating that lipopolysaccharide (LPS)-induced upregulation of the inflammasome/IL-1 beta pathway is accompanied with an increased inflammatory response and abnormal lipid accumulation in livers of aged rats. To monitor the effects of aging on LPS-induced inflammation, we administered LPS (2 mg kg(-1)) to young (6-month old) and aged (24-month old) rats and found abnormal lipid metabolism in only aged rats with increased lipid accumulation in the liver. This lipid accumulation in the liver was due to the dysregulation of PPAR alpha and SREBP1c. We also observed severe liver inflammation in aged rats as indicated by increased ALT levels in serum and increased Kupffer cells in the liver. Importantly, among many inflammation-associated factors, the aged rat liver showed chronically increased IL-1 beta production. Increased levels of IL-1 beta were caused by the upregulation of caspase-1 activity and inflammasome activation. In vitro studies with HepG2 cells demonstrated that treatment with IL-1 beta significantly induced lipid accumulation in hepatocytes through the regulation of PPAR alpha and SREBP1c. In summary, we demonstrated that LPS-induced liver inflammation and lipid accumulation were associated with a chronically overactive inflammasome/IL-1 beta pathway in aged rat livers. Based on the present findings, we propose a mechanism of aging-associated progression of steatohepatitis induced by endotoxin, delineating a pathogenic role of the inflammasome/IL-beta b pathway involved in lipid accumulation in the liver.
机译：衰老与增加对炎性挑战的脆弱性有关。然而，炎症反应改变对组织或器官的代谢状态的影响尚未得到充分证明。在这项研究中，我们目前的证据表明脂多糖（LPS）诱导的炎性小体/ IL-1β途径上调伴随着炎症反应的增加和老年大鼠肝脏中脂质的异常蓄积。为了监测衰老对LPS诱导的炎症的影响，我们向年轻（6个月大）和年老（24个月大）大鼠施用了LPS（2 mg kg（-1）），仅在老龄大鼠中发现脂质代谢异常肝脏中脂质积累增加。肝脏中这种脂质的积累是由于PPARα和SREBP1c的失调所致。我们还观察到老年大鼠出现严重的肝脏炎症，如血清中ALT水平升高和肝脏中Kupffer细胞增多所表明。重要的是，在许多炎症相关因素中，衰老的大鼠肝脏显示出IL-1β产生的慢性增加。 IL-1β的水平升高是由caspase-1活性上调和炎症小体激活引起的。对HepG2细胞的体外研究表明，用IL-1β处理可通过调节PPARα和SREBP1c显着诱导脂质在肝细胞中的蓄积。总之，我们证明了LPS诱导的肝脏炎症和脂质蓄积与衰老大鼠肝脏中的慢性过度活跃的炎症小体/ IL-1β途径有关。基于目前的发现，我们提出了内毒素诱导的脂肪性肝炎与衰老相关的进展的机制，描绘了炎性小体/IL-βb通路参与肝脏脂质蓄积的致病作用。

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