O-GlcNAc Modification of CEBPB Promotes Astrocytic Pyroptosis by Activating NLRP3 Inflammasome Through Transcriptional Activation of IKKβ
- 1Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province China
- 2Department of Pharmacy, Jiangxi Maternal and Child Health Hospital, Nanchang 330008, Jiangxi Province China
Abstract
Major depressive disorder (MDD) is associated with astrocytic pyroptosis, but the mechanisms involved remain unclear. This study investigates how O-GlcNAc modification of CCAAT enhancer binding protein beta (CEBPB) influences its ability to regulate pyroptosis in astrocytes. In our study, primary astrocytes were exposed to LPS plus ATP to activate NLRP3 inflammasomes. Cell viability was assessed by CCK8 assay. IL-18 and IL-1β release was measured using ELISA. sWGA pull-down and Co-IP assays were performed to assess O-GlcNAc modification level of CEBPB. ChIP assay was used for promoter binding analysis, and ubiquitination detection was performed using Co-IP. Our results showed that LPS+ATP treatment significantly increased IKKβ expression in astrocytes, and IKKβ knockdown markedly reduced NLRP3 inflammasome activity and pyroptosis. Mechanistically, CEBPB transcriptionally activated IKKβ expression in astrocytes. Functionally, CEBPB knockdown ameliorated LPS+ATP-induced NLRP3 inflammasome activation and pyroptosis in astrocytes, which was abolished by IKKβ overexpression. In addition, O-GlcNAc modification at Thr235 enhanced CEBPB protein stability in astrocytes, driving NLRP3 inflammasome activation and pyroptosis. Collectively, these findings demonstrated that O-GlcNAc-modified CEBPB promoted pyroptosis in astrocytes during MDD progression by activating NLRP3 inflammasome through transcriptionally activating IKKβ.
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BibTeX
@article{gu2026oglcnac,
title = {{O-GlcNAc Modification of CEBPB Promotes Astrocytic Pyroptosis by Activating NLRP3 Inflammasome Through Transcriptional Activation of IKKβ}},
author = {Xunhu Gu and Yufeng Chen and Lili Zheng and Xu Liu and Yanping Li and Shenjian Chen and Ruiqing Luo and Ming Li and Wei Wang},
journal = {Experimental Neurobiology},
year = {2026},
month = oct,
doi = {10.5607/en26004},
url = {https://doi.org/10.5607/en26004},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - O-GlcNAc Modification of CEBPB Promotes Astrocytic Pyroptosis by Activating NLRP3 Inflammasome Through Transcriptional Activation of IKKβ
AU - Xunhu Gu
AU - Yufeng Chen
AU - Lili Zheng
AU - Xu Liu
AU - Yanping Li
AU - Shenjian Chen
AU - Ruiqing Luo
AU - Ming Li
AU - Wei Wang
PY - 2026
DA - 2026/10/31
JO - Experimental Neurobiology
DO - 10.5607/en26004
UR - https://doi.org/10.5607/en26004
AB - Major depressive disorder (MDD) is associated with astrocytic pyroptosis, but the mechanisms involved remain unclear. This study investigates how O-GlcNAc modification of CCAAT enhancer binding protein beta (CEBPB) influences its ability to regulate pyroptosis in astrocytes. In our study, primary astrocytes were exposed to LPS plus ATP to activate NLRP3 inflammasomes. Cell viability was assessed by CCK8 assay. IL-18 and IL-1β release was measured using ELISA. sWGA pull-down and Co-IP assays were performed to assess O-GlcNAc modification level of CEBPB. ChIP assay was used for promoter binding analysis, and ubiquitination detection was performed using Co-IP. Our results showed that LPS+ATP treatment significantly increased IKKβ expression in astrocytes, and IKKβ knockdown markedly reduced NLRP3 inflammasome activity and pyroptosis. Mechanistically, CEBPB transcriptionally activated IKKβ expression in astrocytes. Functionally, CEBPB knockdown ameliorated LPS+ATP-induced NLRP3 inflammasome activation and pyroptosis in astrocytes, which was abolished by IKKβ overexpression. In addition, O-GlcNAc modification at Thr235 enhanced CEBPB protein stability in astrocytes, driving NLRP3 inflammasome activation and pyroptosis. Collectively, these findings demonstrated that O-GlcNAc-modified CEBPB promoted pyroptosis in astrocytes during MDD progression by activating NLRP3 inflammasome through transcriptionally activating IKKβ.
SN - 1226-2560
SN - 2093-8144
ER -