دورية أكاديمية

Isoliquiritigenin limits inflammasome activation of macrophage via docking into Syk to alleviate murine non-alcoholic fatty liver disease.

التفاصيل البيبلوغرافية
العنوان: Isoliquiritigenin limits inflammasome activation of macrophage via docking into Syk to alleviate murine non-alcoholic fatty liver disease.
المؤلفون: Hu X; Department of Gastroenterology, Yangzhou Key Laboratory for Precision Treatment of Refractory Bowel Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.; Department of Basic Medicine, School of Medicine, Yangzhou University, Yangzhou, China., Hu C; Department of Basic Medicine, School of Medicine, Yangzhou University, Yangzhou, China., Liao L; Department of Basic Medicine, School of Medicine, Yangzhou University, Yangzhou, China., Zhang H; Department of Basic Medicine, School of Medicine, Yangzhou University, Yangzhou, China., Xu X; Department of Gastroenterology, Yangzhou Key Laboratory for Precision Treatment of Refractory Bowel Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China., Xiang J; Department of Pharmacology, School of Medicine, Yangzhou University, Yangzhou, China., Lu G; Department of Gastroenterology, Yangzhou Key Laboratory for Precision Treatment of Refractory Bowel Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.; Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China., Jia X; Department of Basic Medicine, School of Medicine, Yangzhou University, Yangzhou, China., Xu H; Kunshan Hospital of Traditional Chinese Medicine, Kunshan Affiliated Hospital of Yangzhou University, Kunshan, China., Gong W; Department of Gastroenterology, Yangzhou Key Laboratory for Precision Treatment of Refractory Bowel Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.; Department of Basic Medicine, School of Medicine, Yangzhou University, Yangzhou, China.; Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, China.; Jiangsu Key Laboratory of Zoonosis, Yangzhou, China.
المصدر: Scandinavian journal of immunology [Scand J Immunol] 2024 Jul; Vol. 100 (1), pp. e13371. Date of Electronic Publication: 2024 Apr 26.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Blackwell Scientific Publications Country of Publication: England NLM ID: 0323767 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-3083 (Electronic) Linking ISSN: 03009475 NLM ISO Abbreviation: Scand J Immunol Subsets: MEDLINE
أسماء مطبوعة: Publication: Oxford : Blackwell Scientific Publications
Original Publication: Oslo, Universitetsforlaget.
مواضيع طبية MeSH: Syk Kinase*/metabolism , Chalcones*/pharmacology , Inflammasomes*/metabolism , Inflammasomes*/drug effects , Macrophages*/immunology , Macrophages*/metabolism , Macrophages*/drug effects , Non-alcoholic Fatty Liver Disease*/drug therapy , Non-alcoholic Fatty Liver Disease*/metabolism , Non-alcoholic Fatty Liver Disease*/immunology , Mice, Transgenic*, Animals ; Mice ; Macrophage Activation/drug effects ; Mice, Inbred C57BL ; Molecular Docking Simulation ; Male ; Phosphorylation ; Disease Models, Animal
مستخلص: Isoliquiritigenin (ISL) is a chalcone-type flavonoid derived from the root of licorice with antioxidant, anti-inflammatory, anti-tumour and neuroprotective properties. ISL has been proven to downregulate the productions of IL-1β, TNF-α and IL-6 by macrophages. However, detailed molecular mechanisms of this modulation remain elusive. Here, ISL suppressed Syk phosphorylation and CD80, CD86, IL-1β, TNF-α and IL-6 expressions in lipopolysaccharide-stimulated macrophages ex vivo. ApoC3-transgenic (ApoC3 TG ) mice had more activated macrophages. ISL was also able to downregulate the inflammatory activities of macrophages from ApoC3 TG mice. Administration of ISL inhibited Syk activation and inflammatory activities of macrophages in ApoC3 TG mice in vivo. The treatment of ISL further alleviated MCD-induced non-alcoholic fatty liver disease (NAFLD) in wild-type and ApoC3 TG mice, accompanied by less recruitment and activation of liver macrophages. Due to the inhibition of Syk phosphorylation, ISL-treated macrophages displayed less production of cytoplasmic ROS, NLRP3, cleaved-GSDMD and cleaved-IL-1β, suggesting less inflammasome activation. Finally, the molecular docking study demonstrated that ISL bound to Syk directly with the K d of 1.273 × 10 -8  M. When the Syk expression was knocked down by its shRNA, the inhibitory effects of ISL on activated macrophages disappeared, indicating that Syk was at least one of key docking-molecules of ISL. Collectively, ISL could alleviate MCD-induced NAFLD in mice involved with the inhibition of macrophage inflammatory activity by the blockade of Syk-induced inflammasome activation.
(© 2024 The Scandinavian Foundation for Immunology.)
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معلومات مُعتمدة: 82272809 National Natural Science Foundation of China; 82241043 National Natural Science Foundation of China; 81873866 National Natural Science Foundation of China; 81873867 National Natural Science Foundation of China; BE2022775 Social Development Foundation of Jiangsu Province, China; YZ2023248 Cultivation Foundation of Yangzhou Municipal Key Laboratory
فهرسة مساهمة: Keywords: NAFLD; Syk; inflammasome; isoliquiritigenin; macrophage
المشرفين على المادة: B9CTI9GB8F (isoliquiritigenin)
EC 2.7.10.2 (Syk Kinase)
0 (Chalcones)
0 (Inflammasomes)
EC 2.7.10.2 (Syk protein, mouse)
تواريخ الأحداث: Date Created: 20240427 Date Completed: 20240610 Latest Revision: 20240610
رمز التحديث: 20240610
DOI: 10.1111/sji.13371
PMID: 38671579
قاعدة البيانات: MEDLINE
الوصف
تدمد:1365-3083
DOI:10.1111/sji.13371