NF-κB-mediated regulation of rat CYP2E1 by two independent signaling pathways
| Autor: | Fengting Liu, Jinxue Jia, Xue-feng Li, Yongzhi Xue, Tao Wang, Xiao-lin Kang, Ziqi Jin, Qin Lin |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Physiology Gene Expression Nitric Oxide Synthase Type II Pathology and Laboratory Medicine Rats Sprague-Dawley Mathematical and Statistical Techniques 0302 clinical medicine Drug Metabolism Immune Physiology Medicine and Health Sciences Enzyme-Linked Immunoassays Immune Response Liver injury Innate Immune System Multidisciplinary medicine.diagnostic_test Chemistry Liver Diseases Transcriptional Control Statistics Fatty liver NF-kappa B Interleukin Cytochrome P-450 CYP2E1 CYP2E1 Mycobacterium bovis Body Fluids Up-Regulation Blood Liver 030220 oncology & carcinogenesis Physical Sciences Medicine Cytokines Tumor necrosis factor alpha Anatomy Chemical and Drug Induced Liver Injury medicine.symptom Research Article Signal Transduction Transcriptional Activation medicine.medical_specialty Science Immunology Inflammation Gastroenterology and Hepatology Research and Analysis Methods Blood Plasma Proinflammatory cytokine 03 medical and health sciences Signs and Symptoms Western blot Diagnostic Medicine Internal medicine Genetics medicine Animals Humans Pharmacokinetics Gene Regulation Statistical Methods Immunoassays Pharmacology Analysis of Variance Ethanol Biology and Life Sciences Molecular Development medicine.disease Rats Fatty Liver Disease Models Animal 030104 developmental biology Endocrinology Immune System Immunologic Techniques Mathematics Developmental Biology |
| Zdroj: | PLoS ONE PLoS ONE, Vol 14, Iss 12, p e0225531 (2019) |
| ISSN: | 1932-6203 |
| Popis: | Cytochrome P450 2E1 (CYP2E1) plays an important role in both alcohol-induced and immune-mediated liver injury. However, the mechanism underlying CYP2E1 transcriptional regulation has not been clarified. This study focused on the NF-κB-mediated transcriptional regulation of rat CYP2E1 by two independent signaling pathways in alcohol-induced and immune-mediated liver injury rat models. Male Sprague-Dawley rats were used in pharmacokinetic, molecular pharmacology, and morphology experiments. A rat model of alcohol-induced liver injury (AL) was established by feeding an ethanol-containing diet (42 g/kg/day) for 5 weeks as indicated. A rat immune-mediated liver injury (IM) model was established by the sequential injection of bacillus Calmette-Guérin (BCG, 125 mg/kg, once) via the tail vein after test day 21 and 10 μg/kg LPS 13 days later. HPLC, real-time PCR, western blot and ELISA analyses were performed. CYP2E1 expression was enhanced during the process of alcohol-induced liver injury (increased by 56%, P < 0.05) and significantly reduced during that of immune-mediated liver injury (reducedby52%, P < 0.05). NF-κB was activated in both the AL and IM groups (increased by 56% and76%, respectively, P < 0.05). Compared to those in the livers of AL model rats, the interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and iNOS levels in IM model rat livers were increased (increased by 26%, 21% and 101%, respectively, P < 0.05). The differential changes in CYP2E1 in the processes of alcohol-induced and immune-mediated liver injury may result from the differential expression of inflammatory cytokines and iNOS after NF-κB activation, leading to the NF-κB-mediated transcriptional regulation of rat CYP2E1 by two independent signaling pathways. |
| Databáze: | OpenAIRE |
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