CXCR4-BTK axis mediate pyroptosis and lipid peroxidation in early brain injury after subarachnoid hemorrhage via NLRP3 inflammasome and NF-κB pathway
C-X-C chemokine receptor type 4 (CXCR4) is critical for homeostasis of the adaptive and innate immune system in some CNS diseases. Bruton's tyrosine kinase (BTK) is an essential kinase that regulates inflammation in immune cells through multiple signaling pathways. This study aims to explore th...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231723003610 |
| _version_ | 1827596456863727616 |
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| author | Chengli Liu Kun Yao Qi Tian Yujia Guo Guijun Wang Peibang He Jianfeng Wang Jian Wang Zhan Zhang Mingchang Li |
| author_facet | Chengli Liu Kun Yao Qi Tian Yujia Guo Guijun Wang Peibang He Jianfeng Wang Jian Wang Zhan Zhang Mingchang Li |
| author_sort | Chengli Liu |
| collection | DOAJ |
| description | C-X-C chemokine receptor type 4 (CXCR4) is critical for homeostasis of the adaptive and innate immune system in some CNS diseases. Bruton's tyrosine kinase (BTK) is an essential kinase that regulates inflammation in immune cells through multiple signaling pathways. This study aims to explore the effect of CXCR4 and BTK on neuroinflammation in the pathogenesis of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Our results showed that the expression of CXCR4 and p-BTK increased significantly at 24 h after SAH in vivo and in vitro. Ibrutinib improved neurological impairment, BBB disruption, cerebral edema, lipid peroxidation, neuroinflammation and neuronal death at 24 h after SAH. Inhibition of BTK phosphorylation promoted the in vitro transition of hemin-treated proinflammatory microglia to the anti-inflammatory state, inhibited the p-P65 expression and microglial pyroptosis. NLRP3 deficiency can significantly reduce pyroptosis in SAH mice. Moreover, CXCR4 inhibition can suppress NLRP3-mediated pyroptosis, NF-κB activation and NOX2 expression in vitro, and ibrutinib can abolish CXCR4-aggravated BBB damage and pyroptosis in EBI after SAH. The levels of CXCR4 in CSF of SAH patients is significantly increased, and it is positively correlated with GSDMD and IL-1β levels, and have a moderate diagnostic value for outcome at 6-month follow-up. Our findings revealed the effect of CXCR4 and P-BTK on NLRP3-mediated pyroptosis and lipid peroxidation after SAH in vivo and in vitro, and the potential diagnostic role of CXCR4 in CSF of SAH patients. Inhibition of CXCR4-BTK axis can significantly attenuate NLRP3-mediated pyroptosis and lipid peroxidation by regulating NF-κB activation in EBI after SAH. |
| first_indexed | 2024-03-09T03:10:49Z |
| format | Article |
| id | doaj.art-44566a394be64a41a3d18a6dee3231b4 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-03-09T03:10:49Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-44566a394be64a41a3d18a6dee3231b42023-12-04T05:21:50ZengElsevierRedox Biology2213-23172023-12-0168102960CXCR4-BTK axis mediate pyroptosis and lipid peroxidation in early brain injury after subarachnoid hemorrhage via NLRP3 inflammasome and NF-κB pathwayChengli Liu0Kun Yao1Qi Tian2Yujia Guo3Guijun Wang4Peibang He5Jianfeng Wang6Jian Wang7Zhan Zhang8Mingchang Li9Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, PR ChinaDepartment of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, PR ChinaDepartment of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, PR ChinaDepartment of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, PR ChinaDepartment of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, PR ChinaDepartment of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, PR ChinaDepartment of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, PR ChinaDepartment of Anatomy, College of Basic Medical Sciences, Zhengzhou University, Henan, 450000, PR ChinaDepartment of Rehabilitation Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, PR China; Corresponding author. Department of Rehabilitation Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, PR China.Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, PR China; Corresponding author. Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, PR China.C-X-C chemokine receptor type 4 (CXCR4) is critical for homeostasis of the adaptive and innate immune system in some CNS diseases. Bruton's tyrosine kinase (BTK) is an essential kinase that regulates inflammation in immune cells through multiple signaling pathways. This study aims to explore the effect of CXCR4 and BTK on neuroinflammation in the pathogenesis of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Our results showed that the expression of CXCR4 and p-BTK increased significantly at 24 h after SAH in vivo and in vitro. Ibrutinib improved neurological impairment, BBB disruption, cerebral edema, lipid peroxidation, neuroinflammation and neuronal death at 24 h after SAH. Inhibition of BTK phosphorylation promoted the in vitro transition of hemin-treated proinflammatory microglia to the anti-inflammatory state, inhibited the p-P65 expression and microglial pyroptosis. NLRP3 deficiency can significantly reduce pyroptosis in SAH mice. Moreover, CXCR4 inhibition can suppress NLRP3-mediated pyroptosis, NF-κB activation and NOX2 expression in vitro, and ibrutinib can abolish CXCR4-aggravated BBB damage and pyroptosis in EBI after SAH. The levels of CXCR4 in CSF of SAH patients is significantly increased, and it is positively correlated with GSDMD and IL-1β levels, and have a moderate diagnostic value for outcome at 6-month follow-up. Our findings revealed the effect of CXCR4 and P-BTK on NLRP3-mediated pyroptosis and lipid peroxidation after SAH in vivo and in vitro, and the potential diagnostic role of CXCR4 in CSF of SAH patients. Inhibition of CXCR4-BTK axis can significantly attenuate NLRP3-mediated pyroptosis and lipid peroxidation by regulating NF-κB activation in EBI after SAH.http://www.sciencedirect.com/science/article/pii/S2213231723003610Subarachnoid hemorrhageNeuroinflammationPyroptosisBTKCXCR4Lipid peroxidation |
| spellingShingle | Chengli Liu Kun Yao Qi Tian Yujia Guo Guijun Wang Peibang He Jianfeng Wang Jian Wang Zhan Zhang Mingchang Li CXCR4-BTK axis mediate pyroptosis and lipid peroxidation in early brain injury after subarachnoid hemorrhage via NLRP3 inflammasome and NF-κB pathway Redox Biology Subarachnoid hemorrhage Neuroinflammation Pyroptosis BTK CXCR4 Lipid peroxidation |
| title | CXCR4-BTK axis mediate pyroptosis and lipid peroxidation in early brain injury after subarachnoid hemorrhage via NLRP3 inflammasome and NF-κB pathway |
| title_full | CXCR4-BTK axis mediate pyroptosis and lipid peroxidation in early brain injury after subarachnoid hemorrhage via NLRP3 inflammasome and NF-κB pathway |
| title_fullStr | CXCR4-BTK axis mediate pyroptosis and lipid peroxidation in early brain injury after subarachnoid hemorrhage via NLRP3 inflammasome and NF-κB pathway |
| title_full_unstemmed | CXCR4-BTK axis mediate pyroptosis and lipid peroxidation in early brain injury after subarachnoid hemorrhage via NLRP3 inflammasome and NF-κB pathway |
| title_short | CXCR4-BTK axis mediate pyroptosis and lipid peroxidation in early brain injury after subarachnoid hemorrhage via NLRP3 inflammasome and NF-κB pathway |
| title_sort | cxcr4 btk axis mediate pyroptosis and lipid peroxidation in early brain injury after subarachnoid hemorrhage via nlrp3 inflammasome and nf κb pathway |
| topic | Subarachnoid hemorrhage Neuroinflammation Pyroptosis BTK CXCR4 Lipid peroxidation |
| url | http://www.sciencedirect.com/science/article/pii/S2213231723003610 |
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