Rab11b promotes M1-like macrophage polarization by restraining autophagic degradation of NLRP3 in alcohol-associated liver disease  

作　　者：Yu-xin Zhao Ying-yin Sun Liang-yun Li Xiao-feng Li Hai-di Li Xin Chen Ran Xia Ying-Li Yang Xin-yu Jiang Long-quan Zuo Xiao-ming Meng Hua Wang Cheng Huang Jun Li 

机构地区：[1]Inflammation and Immune Mediated Diseases Laboratory of Anhui Province,Anhui Institute of Innovative Drugs,School of Pharmacy,Anhui Medical University,Hefei 230032,China [2]Key Laboratory of Anti-inflammatory and Immune Medicines,Ministry of Education,Anhui Medical University,Hefei 230032,China [3]Institute for Liver Diseases of Anhui Medical University,ILD-AMU,Anhui Medical University,Hefei 230032,China [4]Department of Oncology,the First Affiliated Hospital of Anhui Medical University,Hefei 230032,China [5]The Second School of Clinical Medicine,Anhui Medical University,Hefei 230032,China [6]Department of Pharmacy,Hospital of Armed Police of Anhui Province,Hefei 230032,China

出　　处：《Acta Pharmacologica Sinica》2025年第1期134-146,共13页中国药理学报(英文版)

基　　金：This project was supported by the National Natural Science Foundation of China(82370630,82100627,82300722);Research Fund of Anhui Institute of Translational Medicine(2021zhyx-B06,2022zhyx-B07);Natural Science Foundation of Anhui Province(2108085QH311,2308085QH248);China Postdoctoral Science Foundation(2022M710178);Anhui Fund for Distinguished Young Scholars(2022AH020050);Postgraduate Innovation Research and Practice Program of Anhui Medical University(YJS20230056);Scientific Research Promotion Fund of Anhui Medical University(2022xkjT010);Scientific Research Platform Improvement Project of Anhui Medical University(2022xkjT045).

摘　　要：Macrophage polarization is vital to mounting a host defense or repairing tissue in various liver diseases.Excessive activation of the NLR family pyrin domain containing 3(NLRP3)inflammasome is related to the orchestration of inflammation and alcohol-associated liver disease(ALD)pathology.Rab GTPases play critical roles in regulating vesicular transport.In this study we investigated the role of Rab11b in ALD,aiming to identify effective therapeutic targets.Here,we first demonstrated a decreased expression of Rab11b in macrophages from ALD mice.Knockdown of Rab11b by macrophage-specific adeno-associated virus can alleviate alcohol induced liver inflammation,injury and steatosis.Wefound that LPS and alcohol stimulation promoted Rab11b transferring from the nucleus to the cytoplasm in bone marrow-derived macrophages(BMDM)cells.Rab11b specifically activated the NLRP3 inflammasome in BMDMs and RAW264.7 cells to induce M1 macrophage polarization.Rab11b overexpression in BMDMs inhibited autophagic flux,leading to the suppression of LC3B-mediated NLRP3 degradation.We conclude that impaired Rab11b could alleviate alcoholinduced liver injury via autophagy-mediated NLRP3 degradation.

关 键 词：ALD NLRP3 AUTOPHAGY Rab11b inflammation 

分 类 号：R57[医药卫生—消化系统]