Cargando…

Kakonein restores hyperglycemia‐induced macrophage digestion dysfunction through regulation of cathepsin B‐dependent NLRP3 inflammasome activation

In hyperglycemia‐induced complications, macrophages play important roles in disease progression, and altered digestion is a key feature that dictates macrophage function. Recent evidence indicates that kakonein (Ka) possesses anti‐inflammatory activities for hyperglycemia‐induced complication. In th...

Descripción completa

Detalles Bibliográficos
Autores principales: Lian, Dawei, Zhu, Li, Yu, Yunhong, Zhang, Xiaojuan, Lin, Yike, Liu, Jiaying, Han, Ruifang, Guo, Yitong, Cai, Dongpeng, Xiao, Wenjing, Chen, Yulin, He, Hong, Xu, Danping, Zheng, Chaoyang, Wang, Xiao, Huang, Yi, Chen, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305139/
https://www.ncbi.nlm.nih.gov/pubmed/35224772
http://dx.doi.org/10.1002/JLB.3MA0821-418R
_version_ 1784752251928051712
author Lian, Dawei
Zhu, Li
Yu, Yunhong
Zhang, Xiaojuan
Lin, Yike
Liu, Jiaying
Han, Ruifang
Guo, Yitong
Cai, Dongpeng
Xiao, Wenjing
Chen, Yulin
He, Hong
Xu, Danping
Zheng, Chaoyang
Wang, Xiao
Huang, Yi
Chen, Yang
author_facet Lian, Dawei
Zhu, Li
Yu, Yunhong
Zhang, Xiaojuan
Lin, Yike
Liu, Jiaying
Han, Ruifang
Guo, Yitong
Cai, Dongpeng
Xiao, Wenjing
Chen, Yulin
He, Hong
Xu, Danping
Zheng, Chaoyang
Wang, Xiao
Huang, Yi
Chen, Yang
author_sort Lian, Dawei
collection PubMed
description In hyperglycemia‐induced complications, macrophages play important roles in disease progression, and altered digestion is a key feature that dictates macrophage function. Recent evidence indicates that kakonein (Ka) possesses anti‐inflammatory activities for hyperglycemia‐induced complication. In this study, we established a mouse model of Nlrp3(+/+) and Nlrp3(−/−) hyperglycemia and administering Ka, primary culture macrophages were tested by engulfing and digesting microbes. The role of macrophages in the cathepsin B–NLRP3 pathway involved in the mechanism of Ka in restoring macrophage digestion function was investigated using biochemical analyses, molecular biotechnology, and microbiology. Ka restored the function of macrophage digestion, which were same characterized by Nlrp3(−/−) mice. Meanwhile, kakonein could decrease NLRP3 inflammasome products expression and NLRP3/ASC or NLRP3/Casp1 colocalization in macrophage. Interestingly, Ka suppressed inflammasome response not by reducing NLRP3 and ASC expression but by reducing cathepsin B release and activation. And Ka restored macrophage digestion and inhibited NLRP3 inflammasome activation consistent with cathepsin B inhibitor. It is concluded that Ka reduced the release of lysosomal cathepsin B and consequently inhibited NLRP3 inflammasome activation to prevent macrophage digestion. Hence, Ka may contribute to new targets for treatment of hyperglycemia‐associated dysfunction of macrophage digestion and development of innovative drugs.
format Online
Article
Text
id pubmed-9305139
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-93051392022-07-28 Kakonein restores hyperglycemia‐induced macrophage digestion dysfunction through regulation of cathepsin B‐dependent NLRP3 inflammasome activation Lian, Dawei Zhu, Li Yu, Yunhong Zhang, Xiaojuan Lin, Yike Liu, Jiaying Han, Ruifang Guo, Yitong Cai, Dongpeng Xiao, Wenjing Chen, Yulin He, Hong Xu, Danping Zheng, Chaoyang Wang, Xiao Huang, Yi Chen, Yang J Leukoc Biol Guest Editors: Lian Zhou, Yuejuan Zheng, Yang Chen, Chengfang Yao, Yuhong Bian In hyperglycemia‐induced complications, macrophages play important roles in disease progression, and altered digestion is a key feature that dictates macrophage function. Recent evidence indicates that kakonein (Ka) possesses anti‐inflammatory activities for hyperglycemia‐induced complication. In this study, we established a mouse model of Nlrp3(+/+) and Nlrp3(−/−) hyperglycemia and administering Ka, primary culture macrophages were tested by engulfing and digesting microbes. The role of macrophages in the cathepsin B–NLRP3 pathway involved in the mechanism of Ka in restoring macrophage digestion function was investigated using biochemical analyses, molecular biotechnology, and microbiology. Ka restored the function of macrophage digestion, which were same characterized by Nlrp3(−/−) mice. Meanwhile, kakonein could decrease NLRP3 inflammasome products expression and NLRP3/ASC or NLRP3/Casp1 colocalization in macrophage. Interestingly, Ka suppressed inflammasome response not by reducing NLRP3 and ASC expression but by reducing cathepsin B release and activation. And Ka restored macrophage digestion and inhibited NLRP3 inflammasome activation consistent with cathepsin B inhibitor. It is concluded that Ka reduced the release of lysosomal cathepsin B and consequently inhibited NLRP3 inflammasome activation to prevent macrophage digestion. Hence, Ka may contribute to new targets for treatment of hyperglycemia‐associated dysfunction of macrophage digestion and development of innovative drugs. John Wiley and Sons Inc. 2022-02-27 2022-07 /pmc/articles/PMC9305139/ /pubmed/35224772 http://dx.doi.org/10.1002/JLB.3MA0821-418R Text en © 2022 The Authors. Journal of Leukocyte Biology published by Wiley Periodicals LLC on behalf of Society for Leukocyte Biology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Guest Editors: Lian Zhou, Yuejuan Zheng, Yang Chen, Chengfang Yao, Yuhong Bian
Lian, Dawei
Zhu, Li
Yu, Yunhong
Zhang, Xiaojuan
Lin, Yike
Liu, Jiaying
Han, Ruifang
Guo, Yitong
Cai, Dongpeng
Xiao, Wenjing
Chen, Yulin
He, Hong
Xu, Danping
Zheng, Chaoyang
Wang, Xiao
Huang, Yi
Chen, Yang
Kakonein restores hyperglycemia‐induced macrophage digestion dysfunction through regulation of cathepsin B‐dependent NLRP3 inflammasome activation
title Kakonein restores hyperglycemia‐induced macrophage digestion dysfunction through regulation of cathepsin B‐dependent NLRP3 inflammasome activation
title_full Kakonein restores hyperglycemia‐induced macrophage digestion dysfunction through regulation of cathepsin B‐dependent NLRP3 inflammasome activation
title_fullStr Kakonein restores hyperglycemia‐induced macrophage digestion dysfunction through regulation of cathepsin B‐dependent NLRP3 inflammasome activation
title_full_unstemmed Kakonein restores hyperglycemia‐induced macrophage digestion dysfunction through regulation of cathepsin B‐dependent NLRP3 inflammasome activation
title_short Kakonein restores hyperglycemia‐induced macrophage digestion dysfunction through regulation of cathepsin B‐dependent NLRP3 inflammasome activation
title_sort kakonein restores hyperglycemia‐induced macrophage digestion dysfunction through regulation of cathepsin b‐dependent nlrp3 inflammasome activation
topic Guest Editors: Lian Zhou, Yuejuan Zheng, Yang Chen, Chengfang Yao, Yuhong Bian
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305139/
https://www.ncbi.nlm.nih.gov/pubmed/35224772
http://dx.doi.org/10.1002/JLB.3MA0821-418R
work_keys_str_mv AT liandawei kakoneinrestoreshyperglycemiainducedmacrophagedigestiondysfunctionthroughregulationofcathepsinbdependentnlrp3inflammasomeactivation
AT zhuli kakoneinrestoreshyperglycemiainducedmacrophagedigestiondysfunctionthroughregulationofcathepsinbdependentnlrp3inflammasomeactivation
AT yuyunhong kakoneinrestoreshyperglycemiainducedmacrophagedigestiondysfunctionthroughregulationofcathepsinbdependentnlrp3inflammasomeactivation
AT zhangxiaojuan kakoneinrestoreshyperglycemiainducedmacrophagedigestiondysfunctionthroughregulationofcathepsinbdependentnlrp3inflammasomeactivation
AT linyike kakoneinrestoreshyperglycemiainducedmacrophagedigestiondysfunctionthroughregulationofcathepsinbdependentnlrp3inflammasomeactivation
AT liujiaying kakoneinrestoreshyperglycemiainducedmacrophagedigestiondysfunctionthroughregulationofcathepsinbdependentnlrp3inflammasomeactivation
AT hanruifang kakoneinrestoreshyperglycemiainducedmacrophagedigestiondysfunctionthroughregulationofcathepsinbdependentnlrp3inflammasomeactivation
AT guoyitong kakoneinrestoreshyperglycemiainducedmacrophagedigestiondysfunctionthroughregulationofcathepsinbdependentnlrp3inflammasomeactivation
AT caidongpeng kakoneinrestoreshyperglycemiainducedmacrophagedigestiondysfunctionthroughregulationofcathepsinbdependentnlrp3inflammasomeactivation
AT xiaowenjing kakoneinrestoreshyperglycemiainducedmacrophagedigestiondysfunctionthroughregulationofcathepsinbdependentnlrp3inflammasomeactivation
AT chenyulin kakoneinrestoreshyperglycemiainducedmacrophagedigestiondysfunctionthroughregulationofcathepsinbdependentnlrp3inflammasomeactivation
AT hehong kakoneinrestoreshyperglycemiainducedmacrophagedigestiondysfunctionthroughregulationofcathepsinbdependentnlrp3inflammasomeactivation
AT xudanping kakoneinrestoreshyperglycemiainducedmacrophagedigestiondysfunctionthroughregulationofcathepsinbdependentnlrp3inflammasomeactivation
AT zhengchaoyang kakoneinrestoreshyperglycemiainducedmacrophagedigestiondysfunctionthroughregulationofcathepsinbdependentnlrp3inflammasomeactivation
AT wangxiao kakoneinrestoreshyperglycemiainducedmacrophagedigestiondysfunctionthroughregulationofcathepsinbdependentnlrp3inflammasomeactivation
AT huangyi kakoneinrestoreshyperglycemiainducedmacrophagedigestiondysfunctionthroughregulationofcathepsinbdependentnlrp3inflammasomeactivation
AT chenyang kakoneinrestoreshyperglycemiainducedmacrophagedigestiondysfunctionthroughregulationofcathepsinbdependentnlrp3inflammasomeactivation