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

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

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Rab11b promotes M1-like macrophage polarization by restraining autophagic degradation of NLRP3 in alcohol-associated liver disease
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.We found 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 alcohol-induced liver injury via autophagy-mediated NLRP3 degradation.

ALDNLRP3autophagyRab11binflammation

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

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Inflammation and Immune Mediated Diseases Laboratory of Anhui Province,Anhui Institute of Innovative Drugs,School of Pharmacy,Anhui Medical University,Hefei 230032,China

Key Laboratory of Anti-inflammatory and Immune Medicines,Ministry of Education,Anhui Medical University,Hefei 230032,China

Institute for Liver Diseases of Anhui Medical University,ILD-AMU,Anhui Medical University,Hefei 230032,China

Department of Oncology,the First Affiliated Hospital of Anhui Medical University,Hefei 230032,China

The Second School of Clinical Medicine,Anhui Medical University,Hefei 230032,China

Department of Pharmacy,Hospital of Armed Police of Anhui Province,Hefei 230032,China

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ALD NLRP3 autophagy Rab11b inflammation

2025

10.1038/s41401-024-01333-5

中国药理学报(英文版)
中科院上海药物研究所

中国药理学报(英文版)

影响因子：0.926
ISSN：1671-4083
年,卷(期)：2025.46(1)