دورية أكاديمية
Endotoxin tolerance ameliorates lipopolysaccharide/D-galactosamine-induced acute liver failure by negative regulation of the NF-κB/NLRP3 and activation of Nrf2/HO-1 via Sitr1.
| العنوان: | Endotoxin tolerance ameliorates lipopolysaccharide/D-galactosamine-induced acute liver failure by negative regulation of the NF-κB/NLRP3 and activation of Nrf2/HO-1 via Sitr1. |
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| المؤلفون: | Shi H; Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China., Xie X; Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China., Zheng S; Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China., Chen H; Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China., Liu C; Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China., Li S; Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China., Lu M; Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address: lmq0906@163.com. |
| المصدر: | International immunopharmacology [Int Immunopharmacol] 2024 May 10; Vol. 132, pp. 111994. Date of Electronic Publication: 2024 Apr 05. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100965259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1705 (Electronic) Linking ISSN: 15675769 NLM ISO Abbreviation: Int Immunopharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam ; New York : Elsevier Science, c2001- |
| مواضيع طبية MeSH: | Galactosamine* , Lipopolysaccharides* , Liver Failure, Acute*/chemically induced , Liver Failure, Acute*/immunology , Liver Failure, Acute*/metabolism , Liver Failure, Acute*/drug therapy , Signal Transduction*/drug effects, Animals ; Male ; Mice ; Disease Models, Animal ; Endotoxins/toxicity ; Heme Oxygenase (Decyclizing)/metabolism ; Heme Oxygenase (Decyclizing)/genetics ; Heme Oxygenase-1/metabolism ; Heme Oxygenase-1/genetics ; Immune Tolerance/drug effects ; Liver/drug effects ; Liver/pathology ; Liver/metabolism ; Liver/immunology ; Macrophages/drug effects ; Macrophages/immunology ; Membrane Proteins/metabolism ; Membrane Proteins/genetics ; Mice, Inbred C57BL ; NF-E2-Related Factor 2/metabolism ; NF-E2-Related Factor 2/genetics ; NF-kappa B/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Oxidative Stress/drug effects ; Pyroptosis/drug effects ; Sirtuin 1/metabolism ; Sirtuin 1/genetics |
| مستخلص: | Acute liver failure (ALF) is a potentially fatal disorder characterized by extensive hepatocyte necrosis and rapid decline in liver function. Numerous factors, including oxidative stress, cell death, and inflammatory responses, are associated with its pathogenesis. Endotoxin tolerance (ET) refers to the phenomenon in which the body or cells exhibit low or no response to high-dose lipopolysaccharide (LPS) stimulation after pre-stimulation with low-dose LPS. However, the specific mechanism through which ET regulates LPS/D-galactosamine (D-GalN)-induced ALF remains unclear. An ALF mouse model was established by intraperitoneal injection of D-GalN (400 mg/kg) and LPS (10 mg/kg). A low dose of LPS (0.1 mg/kg/d) was continuously administered to mice for 5 d before modeling to assess the protective effect of ET. The data from this study showed that ET alleviated the inflammatory response in mice with LPS/D-GalN-induced ALF. ET inhibited LPS-induced oxidative damage and pyroptosis in macrophages in vitro. RNA sequencing analysis showed that the NF-κB/NLRP3 pathway was linked to the anti-inflammatory and antioxidative effects of ET. Furthermore, using western blot, RT-qPCR, and immunofluorescence, we verified that ET inhibited the NF-κB/NLRP3 pathway and triggered the Nrf2/HO-1 signaling pathway to attenuate oxidative stress and cell pyroptosis. Sirt1 knockdown reversed this protective effect. In summary, our research elucidates that ET prevents ALF advancement by upregulating Sirt1 levels, triggering the Nrf2/HO-1 signaling axis, and suppressing the NF-κB/NLRP3 signaling cascade to inhibit oxidative stress and cell pyroptosis. Our results provide a mechanistic explanation for the protective effect of ET against ALF. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Acute liver failure; Endotoxin tolerance; Macrophage; NLRP3 inflammasome; Nrf2; Sirt1 |
| المشرفين على المادة: | 0 (Endotoxins) 7535-00-4 (Galactosamine) EC 1.14.14.18 (Heme Oxygenase (Decyclizing)) EC 1.14.14.18 (Heme Oxygenase-1) EC 1.14.14.18 (Hmox1 protein, mouse) 0 (Lipopolysaccharides) 0 (Membrane Proteins) 0 (NF-E2-Related Factor 2) 0 (NF-kappa B) 0 (Nfe2l2 protein, mouse) 0 (NLR Family, Pyrin Domain-Containing 3 Protein) 0 (Nlrp3 protein, mouse) EC 3.5.1.- (Sirtuin 1) |
| تواريخ الأحداث: | Date Created: 20240406 Date Completed: 20240430 Latest Revision: 20240524 |
| رمز التحديث: | 20240525 |
| DOI: | 10.1016/j.intimp.2024.111994 |
| PMID: | 38581992 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1878-1705 |
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| DOI: | 10.1016/j.intimp.2024.111994 |