Kupffer cells play a crucial role in monocrotaline-induced liver injury by producing TNF-alpha
文献类型：期刊论文
| 作者 | Cao, Yuhan2,3; Liu, Meng2,3; Wu, Shouyan2,3; Xu, Junjiu2,5; Wang, Wenjie2,4; Qi, Xinming2 ; Ren, Jin2,3; Sun, Jianhua2,3; Chen, Jing2,3; Gong, Likun1,2,3
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| 刊名 | TOXICOLOGY
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| 出版日期 | 2022-02-28 |
| 卷号 | 468页码:9 |
| 关键词 | Monocrotaline Kupffer cells Necrosis Hepatotoxicity |
| ISSN号 | 0300-483X |
| DOI | 10.1016/j.tox.2022.153101 |
| 通讯作者 | Chen, Jing(jingchen@simm.ac.cn) ; Gong, Likun(lkgong@cdser.simm.ac.cn) |
| 英文摘要 | Monocrotaline (MCT), an unsaturated pyrrolizidine alkaloid (PA) in plants, is mainly toxic to the lung and liver of mammals. As a commonly used tool for liver injury model, the mechanism of MCT hepatoxicity has still not been fully clarified. Kupffer cells (KCs) are the liver-resident macrophages and have various responses to different toxicants and liver damage. However, the role of KCs in MCT-induced liver injury remains controversial. In current work, we investigated the effects of KCs on MCT-induced liver injury, especially on MCT-induced hepatocyte death. KCs were depleted in Balb/c mice by liposome-entrapped clodronate (Lip/Clo) (0.2 mL/mouse, i.p.) or GdCl3 (0.7 mg/kg, i.p.) before MCT administration (300 mg/kg, i.p.), we found that the Lip/ CM group showed higher efficiency in KCs depletion and stronger hepatoprotective effects against MCT. We also found TNF-alpha was remarkably decreased after KCs depletion, the experiment of administering anti-TNF-alpha antibody (20 mu g/mouse, i.p.) to MCT-treated animals generated the similar results. To further elaborate the function of KCs, we compared the ALT levels released from co-culturing murine hepatic parenchymal cells (HPCs) and RAW264.7 cells with that from HPCs alone. After the treatment of MCT, the released ALT levels in co-culture system were shown to be dependent on the number of RAW264.7 cells, while the anti-TNF-alpha antibody could suppress it. Finally, we discovered RIPK3/MLKL pathway might be activated by TNF-alpha released from KCs, and subsequently induced hepatocyte necrosis. Noteworthy, the known mechanisms including ER stress and NF-kappa B pathways were also found to be involved in the activation of KCs. In conclusion, our study reveals a further mechanism to MCT-induced hepatoxicity mediated directly by KCs via producing TNF-alpha. |
| WOS关键词 | HEPATIC VENOOCCLUSIVE DISEASE ; PYRROLIZIDINE ALKALOIDS ; NORTHERN AUSTRALIA ; IN-VITRO ; INFLAMMATION ; ACTIVATION ; LIPOSOMES ; DEPLETION ; MICE ; RAT |
| 资助项目 | Department of Science and Technology of Zhongshan City[2020SYF08] ; Post-Doctoral Science Foundation of China[2020499] ; Guangdong Province Science and Technology Plan Project[2019B020202003] ; Foundation of Shanghai Science and Technology Committee[21DZ2291100] |
| WOS研究方向 | Pharmacology & Pharmacy ; Toxicology |
| 语种 | 英语 |
| WOS记录号 | WOS:000754423200001 |
| 出版者 | ELSEVIER IRELAND LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/300312]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Chen, Jing; Gong, Likun |
| 作者单位 | 1.Chinese Acad Sci, Inst Drug Discovery & Dev, Zhongshan Branch, Beijing, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Fudan Univ, Dept Pharmacol, Shanghai 201203, Peoples R China 5.Nanjing Univ Chinese Med, Nanjing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Cao, Yuhan,Liu, Meng,Wu, Shouyan,et al. Kupffer cells play a crucial role in monocrotaline-induced liver injury by producing TNF-alpha[J]. TOXICOLOGY,2022,468:9. |
| APA | Cao, Yuhan.,Liu, Meng.,Wu, Shouyan.,Xu, Junjiu.,Wang, Wenjie.,...&Gong, Likun.(2022).Kupffer cells play a crucial role in monocrotaline-induced liver injury by producing TNF-alpha.TOXICOLOGY,468,9. |
| MLA | Cao, Yuhan,et al."Kupffer cells play a crucial role in monocrotaline-induced liver injury by producing TNF-alpha".TOXICOLOGY 468(2022):9. |
入库方式： OAI收割
来源：上海药物研究所
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