Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, China.
Mediators Inflamm. 2023 Jan 9;2023:3732315. doi: 10.1155/2023/3732315. eCollection 2023.
LIGHT is a member of the TNF superfamily and a proinflammatory cytokine involved in liver pathogenesis. Many liver diseases involve activation of Toll-like receptor 3 (TLR3), which is activated by double-stranded RNA (dsRNA). However, the involvement of LIGHT in TLR3 implicated liver diseases is not clear. In this study, we investigated the role of LIGHT in TLR3 involved liver pathogenesis by using a mouse model of TLR3 agonist poly(I:C)-induced hepatitis. We found LIGHT expression at both protein and mRNA level in liver tissues is dramatically increased during the course of poly(I:C)-induced liver injury. This induction depends on NF-B activation as pretreating the mice with a NF-B inhibitor abrogates LIGHT upregulation. Importantly, blockade of the LIGHT signaling pathway with the recombinant LIGHT receptor HVEM protein ameliorates liver injury in poly(I:C)-induced hepatitis. . These results indicate that LIGHT amplification by NF-B plays a significant role in TLR3 involved hepatitis and points LIGHT to be a potential drug target for liver disease therapy.
LIGHT 是 TNF 超家族的一员，也是一种参与肝脏发病机制的促炎细胞因子。许多肝脏疾病涉及 Toll 样受体 3（TLR3）的激活，TLR3 被双链 RNA（dsRNA）激活。然而，LIGHT 在 TLR3 参与的肝脏疾病中的作用尚不清楚。在这项研究中，我们通过 TLR3 激动剂 poly（I:C）诱导的肝炎小鼠模型研究了 LIGHT 在 TLR3 参与的肝脏发病机制中的作用。我们发现，在 poly（I:C）诱导的肝损伤过程中，LIGHT 在肝组织中的蛋白和 mRNA 水平均显著增加。这种诱导依赖于 NF-B 的激活，因为用 NF-B 抑制剂预处理小鼠可消除 LIGHT 的上调。重要的是，用重组 LIGHT 受体 HVEM 蛋白阻断 LIGHT 信号通路可改善 poly（I:C）诱导的肝炎中的肝损伤。这些结果表明，NF-B 介导的 LIGHT 扩增在 TLR3 参与的肝炎中起着重要作用，并指出 LIGHT 可能成为肝脏疾病治疗的潜在药物靶点。
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