HIF-1 alpha inhibition in macrophages preserves acute liver failure by reducing IL-1 beta production
文献类型：期刊论文
| 作者 | Kong, Xiangrong1; Liu, Wei2,3; Zhang, Xinwen2; Zhou, Chendong2; Sun, Xinyu2; Cheng, Long2,3; Lin, Jinxia4; Xie, Zhifu2,5; Li, Jingya1,2,3,5
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| 刊名 | FASEB JOURNAL
 |
| 出版日期 | 2023-09-01 |
| 卷号 | 37期号:9页码:12 |
| ISSN号 | 0892-6638 |
| 关键词 | acute liver failure cell death HIF-1 alpha inhibitor interleukin-1 beta macrophage |
| DOI | 10.1096/fj.202300428RR |
| 通讯作者 | Xie, Zhifu(zfxie@simm.ac.cn) ; Li, Jingya(jyli@simm.ac.cn) |
| 英文摘要 | The development of acute liver failure (ALF) is dependent on its local inducer. Inflammation is a high-frequency and critical factor that accelerates hepatocyte death and liver failure. In response to injury stress, the expression of the transcription factor hypoxia-inducible factor-1 alpha (HIF-1 alpha) in macrophages is promoted by both oxygen-dependent and oxygen-independent mechanisms, thus promoting the expression and secretion of the cytokine interleukin-1 beta (IL-1 beta). IL-1 beta further induces hepatocyte apoptosis or necrosis by signaling through the receptor (IL-1R) on hepatocyte. HIF-1 alpha knockout in macrophages or IL-1R knockout in hepatocytes protects against liver failure. However, whether HIF-1 alpha inhibition in macrophages has a protective role in ALF is unclear. In this study, we revealed that the small molecule HIF-1a inhibitor PX-478 inhibits the expression and secretion of IL-1 beta, but not tumor necrosis factor alpha (TNF alpha), in bone marrow-derived macrophages (BMDMs). PX-478 pretreatment alleviates liver injury in LPS/D-GalN-induced ALF mice by decreasing the hepatic inflammatory response. In addition, preventive or therapeutic administration of PX-478 combined with TNF alpha neutralizing antibody markedly improved LPS/D-GalN-induced ALF. Taken together, our data suggest that PX-478 administration leads to HIF-1 alpha inhibition and decreased IL-1 beta secretion in macrophages, which represents a promising therapeutic strategy for inflammation-induced ALF. |
| WOS关键词 | MOLECULAR-MECHANISMS ; INFLAMMATION ; DISEASE ; INJURY ; BNIP3 |
| 资助项目 | National Natural Science Foundation of China[82170872] ; Independent Scientific Research Projects Approved by Institute of Drug Innovation, CAS[CASIMM0120181001] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics ; Cell Biology |
| 语种 | 英语 |
| 出版者 | WILEY |
| WOS记录号 | WOS:001049338200001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/306980]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Xie, Zhifu; Li, Jingya |
| 作者单位 | 1.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China 3.Univ Chinese Acad Sci, Beijing, Peoples R China 4.Zhangzhou Pien Tze Huang Pharmaceut Co Ltd, Zhangzhou, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, 189 GuoShouJing Rd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Kong, Xiangrong,Liu, Wei,Zhang, Xinwen,et al. HIF-1 alpha inhibition in macrophages preserves acute liver failure by reducing IL-1 beta production[J]. FASEB JOURNAL,2023,37(9):12. |
| APA | Kong, Xiangrong.,Liu, Wei.,Zhang, Xinwen.,Zhou, Chendong.,Sun, Xinyu.,...&Li, Jingya.(2023).HIF-1 alpha inhibition in macrophages preserves acute liver failure by reducing IL-1 beta production.FASEB JOURNAL,37(9),12. |
| MLA | Kong, Xiangrong,et al."HIF-1 alpha inhibition in macrophages preserves acute liver failure by reducing IL-1 beta production".FASEB JOURNAL 37.9(2023):12. |
入库方式： OAI收割
来源：上海药物研究所
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