Pretreatment with lipopolysaccharide attenuates diethylnitrosamine-caused liver injury in mice via TLR4-dependent induction of Kupffer cell M2 polarization
Pretreatment with lipopolysaccharide attenuates diethylnitrosamine-caused liver injury in mice via TLR4-dependent induction of Kupffer cell M2 polarization
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DOI：
10.1007/s12026-015-8644-2
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发表时间：
2015-06-01
影响因子：
4.4
通讯作者：
Yang, Yong
中科院分区：
文献类型：
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作者：
Li, Xianjing;Wang, Zhuo;Yang, Yong
本研究发现，低剂量脂多糖（LPS）预处理可明显减轻二乙基亚硝胺（DEN）引起的小鼠肝损伤。这种保护作用通过降低ALT、TNF-α和IL-1 β以及增加TGF-β产生来描述。然而，Toll样受体4缺陷（TLR 4（-/-））或巨噬细胞耗竭在小鼠中消除了这种保护作用，这表明Kupffer细胞（KCs）和TLR 4对于预防LPS对抗DEN诱导的损伤至关重要。进一步研究发现，LPS预处理可诱导KCs向M2极化，并使MAPKs和NF-κ B B信号通路受损，从而导致炎症因子的产生。此外，调节性T细胞（T细胞）也被募集到肝脏，这可能介导免疫抑制，并参与预防DEN诱导的损伤。我们的研究结果表明，LPS通过诱导M2 Kupffer细胞和募集TGFAP来保护DEN诱导的肝炎，这有助于TLR 4依赖性机制中的肝脏耐受。
In this study, we found that pretreatment with low dose of lipopolysaccharide (LPS), also known as lipoglycans and endotoxin, obviously attenuated liver injury caused by diethylnitrosamine (DEN) in mice. This protective effect was described by decreased ALT, TNF-alpha, and IL-1 beta and increased TGF-beta production. However, Toll-like receptor 4-deficient (TLR4(-/-)) or macrophages depletion abolished this protection in mice, which revealed Kupffer cells (KCs) and TLR4 to be crucial for the prevention of LPS against DEN-induced damage. Further study revealed that LPS pretreatment induced the KCs to M2 polarization and impaired the signaling of MAPKs and NF-kappa B that mediated the production of inflammatory cytokines. Moreover, T regulatory cells (Tregs) were also recruited to the liver, which may mediate immunosuppression and participate in the prevention of DEN-induced injury. Our results suggested that LPS protected against DEN-induced hepatitis via induction of M2 Kupffer cells and recruitment of Tregs, which contributes to liver tolerance in TLR4-dependent mechanism.