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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...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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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 |
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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 |
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