The danger signal interferon-induced protein 35 (IFP35) mediates acetaminophen-induced liver injury.
The danger signal interferon-induced protein 35 (IFP35) mediates acetaminophen-induced liver injury.
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DOI：
10.1016/j.bbrc.2022.06.086
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发表时间：
2022-07
影响因子：
3.1
通讯作者：
Xiating Mao;Danning Wu;Na Xu;Jingjing Wang;Jinhua Zeng;Zhiqiang Jiang;Yingfang Liu;Huanhuan Liang
中科院分区：
文献类型：
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作者：
Xiating Mao;Danning Wu;Na Xu;Jingjing Wang;Jinhua Zeng;Zhiqiang Jiang;Yingfang Liu;Huanhuan Liang
过量使用对乙酰氨基酚（APAP）引起的急性肝损伤是一个难以解决的临床问题。坏死肝细胞释放大量细胞内成分，包括损伤相关分子模式（DAMPs），这些成分导致肝衰竭，可能作为治疗靶点。然而，DAMPs在apap诱导的肝损伤（AILI）中的致病机制仍未完全阐明。在这里，我们发现最近发现的一种DAMP，干扰素诱导蛋白35 (IFP35)，参与了AILI的早期阶段。我们的数据表明，尽管IFP35在AILI患者或小鼠中的表达水平没有显著升高，但它从坏死的肝细胞中释放出来。在注射APAP后24小时内，缺乏ifp35的小鼠对APAP诱导的毒性具有抗性，并且诱导的炎症反应比野生型小鼠要少，包括AST/ALT水平降低，促炎细胞因子的产生和中性粒细胞的浸润。更重要的是，IFP35抗体降低了炎症因子和趋化因子的表达水平。本研究对AILI的发病机制有了新的认识。
Acute liver injury caused by overdose usage of acetaminophen (APAP) is an intractable clinical problem. Necrotic hepatocytes release large amounts of intracellular components including damage-associated molecular patterns (DAMPs) which contribute to liver failure and may serve as therapeutic targets. However, the pathogenic mechanisms of DAMPs in APAP-induced liver injury (AILI) are remain largely uncovered. Here, we found that a recently identified DAMP, interferon-induced protein 35 (IFP35), is involved in the early phase of AILI. Our data demonstrated that although the expression level of IFP35 is not significantly increased in either patients or mice with AILI, it is released from necrotic hepatocytes. Within 24 h post APAP injection, mice lackingIfp35are resistant to APAP-induced toxicity, and induce less inflammatory response than that of wild-type mice, including reduced AST/ALT level, pro-inflammatory cytokines production and neutrophils infiltration. More importantly, antibody of IFP35 reduces the expression level of inflammatory factors and chemokines. This study brings new knowledge into the pathogenic mechanism of AILI.