Inhibition of inflammatory liver injury by the HMGB1-A box through HMGB1/TLR-4/NF-κB signaling in an acute liver failure mouse model
We aimed to investigate the preventive effect of high mobility group box 1 (HMGB1)-A box and the mechanism by which it alleviates inflammatory injury in acute liver failure (ALF) by inhibiting the extracellular release of HMGB1. BALB/c mice were intraperitoneally (i.p.) administered LPS/D-GalN to es...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.990087/full |
| _version_ | 1811339396617601024 |
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| author | Lidan Luo Shuai Wang Bohao Chen Mei Zhong Ruili Du ChunShan Wei Furong Huang Furong Huang Xinhui Kou Yufeng Xing Guangdong Tong Guangdong Tong |
| author_facet | Lidan Luo Shuai Wang Bohao Chen Mei Zhong Ruili Du ChunShan Wei Furong Huang Furong Huang Xinhui Kou Yufeng Xing Guangdong Tong Guangdong Tong |
| author_sort | Lidan Luo |
| collection | DOAJ |
| description | We aimed to investigate the preventive effect of high mobility group box 1 (HMGB1)-A box and the mechanism by which it alleviates inflammatory injury in acute liver failure (ALF) by inhibiting the extracellular release of HMGB1. BALB/c mice were intraperitoneally (i.p.) administered LPS/D-GalN to establish an ALF mouse model. HMGB1-A box was administered (i.p.) 1 h before establishing the ALF mouse model. The levels of extracellularly released HMGB1, TLR-4/NF-κB signaling molecules, the proinflammatory cytokines TNF-α, IL-1β, and IL-6 and COX-2 were measured in the liver tissue and/or serum by Immunohistochemistry, Western blotting and Enzyme-linked immunosorbent assay (ELISA). The levels of extracellularly released HMGB1, TLR-4/NF-κB signaling molecules and proinflammatory cytokines were measured in Huh7 cells as well as LPS- and/or HMGB1-A box treatment by confocal microscopy, Western blotting and ELISA. In the ALF mouse model, the levels of HMGB1 were significantly increased both in the liver and serum, TLR-4/NF-κB signaling molecules and proinflammatory cytokines also was upregulated. Notably, HMGB1-A box could reverse these changes. HMGB1-A box could also cause these changes in LPS-induced Huh7 cells. HMGB1-A box played a protective role by inhibiting inflammatory liver injury via the regulation of HMGB1/TLR-4/NF-κB signaling in the LPS/D-GaIN-induced ALF mouse model, which may be related to inhibiting the extracellular release of HMGB1. |
| first_indexed | 2024-04-13T18:25:11Z |
| format | Article |
| id | doaj.art-d5a1b4e59e4748e79d229387732f32ab |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-13T18:25:11Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-d5a1b4e59e4748e79d229387732f32ab2022-12-22T02:35:16ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-10-011310.3389/fphar.2022.990087990087Inhibition of inflammatory liver injury by the HMGB1-A box through HMGB1/TLR-4/NF-κB signaling in an acute liver failure mouse modelLidan Luo0Shuai Wang1Bohao Chen2Mei Zhong3Ruili Du4ChunShan Wei5Furong Huang6Furong Huang7Xinhui Kou8Yufeng Xing9Guangdong Tong10Guangdong Tong11Department of Hepatology, The Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen, ChinaDepartment of Hepatology, The Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen, ChinaDepartment of Hepatology, Shenzhen Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Shenzhen, ChinaDepartment of Hepatology, Shenzhen Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Shenzhen, ChinaDepartment of Hepatology, Shenzhen Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Shenzhen, ChinaDepartment of Hepatology, The Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen, ChinaDepartment of Hepatology, The Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen, ChinaFaculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao, ChinaDepartment of Hepatology, The Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen, ChinaDepartment of Hepatology, The Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen, ChinaDepartment of Hepatology, The Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen, ChinaFaculty of Chinese Medicine and State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao, ChinaWe aimed to investigate the preventive effect of high mobility group box 1 (HMGB1)-A box and the mechanism by which it alleviates inflammatory injury in acute liver failure (ALF) by inhibiting the extracellular release of HMGB1. BALB/c mice were intraperitoneally (i.p.) administered LPS/D-GalN to establish an ALF mouse model. HMGB1-A box was administered (i.p.) 1 h before establishing the ALF mouse model. The levels of extracellularly released HMGB1, TLR-4/NF-κB signaling molecules, the proinflammatory cytokines TNF-α, IL-1β, and IL-6 and COX-2 were measured in the liver tissue and/or serum by Immunohistochemistry, Western blotting and Enzyme-linked immunosorbent assay (ELISA). The levels of extracellularly released HMGB1, TLR-4/NF-κB signaling molecules and proinflammatory cytokines were measured in Huh7 cells as well as LPS- and/or HMGB1-A box treatment by confocal microscopy, Western blotting and ELISA. In the ALF mouse model, the levels of HMGB1 were significantly increased both in the liver and serum, TLR-4/NF-κB signaling molecules and proinflammatory cytokines also was upregulated. Notably, HMGB1-A box could reverse these changes. HMGB1-A box could also cause these changes in LPS-induced Huh7 cells. HMGB1-A box played a protective role by inhibiting inflammatory liver injury via the regulation of HMGB1/TLR-4/NF-κB signaling in the LPS/D-GaIN-induced ALF mouse model, which may be related to inhibiting the extracellular release of HMGB1.https://www.frontiersin.org/articles/10.3389/fphar.2022.990087/fullacute liver failureHMGB1-A boxTLR-4/NF-κB signalingextracellular HMGB1inflammatory injury |
| spellingShingle | Lidan Luo Shuai Wang Bohao Chen Mei Zhong Ruili Du ChunShan Wei Furong Huang Furong Huang Xinhui Kou Yufeng Xing Guangdong Tong Guangdong Tong Inhibition of inflammatory liver injury by the HMGB1-A box through HMGB1/TLR-4/NF-κB signaling in an acute liver failure mouse model Frontiers in Pharmacology acute liver failure HMGB1-A box TLR-4/NF-κB signaling extracellular HMGB1 inflammatory injury |
| title | Inhibition of inflammatory liver injury by the HMGB1-A box through HMGB1/TLR-4/NF-κB signaling in an acute liver failure mouse model |
| title_full | Inhibition of inflammatory liver injury by the HMGB1-A box through HMGB1/TLR-4/NF-κB signaling in an acute liver failure mouse model |
| title_fullStr | Inhibition of inflammatory liver injury by the HMGB1-A box through HMGB1/TLR-4/NF-κB signaling in an acute liver failure mouse model |
| title_full_unstemmed | Inhibition of inflammatory liver injury by the HMGB1-A box through HMGB1/TLR-4/NF-κB signaling in an acute liver failure mouse model |
| title_short | Inhibition of inflammatory liver injury by the HMGB1-A box through HMGB1/TLR-4/NF-κB signaling in an acute liver failure mouse model |
| title_sort | inhibition of inflammatory liver injury by the hmgb1 a box through hmgb1 tlr 4 nf κb signaling in an acute liver failure mouse model |
| topic | acute liver failure HMGB1-A box TLR-4/NF-κB signaling extracellular HMGB1 inflammatory injury |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.990087/full |
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