Propofol Suppresses Microglia Inflammation by Targeting TGM2/NF-κB Signaling
Background. Propofol is a known intravenous hypnotic drug used for induction and maintenance of sedation and general anesthesia. Emerging studies also reveal a neuroprotective effect of propofol in diverse diseases of neuronal injuries via modulating microglia activation. In this study, we aimed to...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2021/4754454 |
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| _version_ | 1849473038064549888 |
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| author | Yuanyuan Hou Xi Xiao Wei Yu Sihua Qi |
| author_facet | Yuanyuan Hou Xi Xiao Wei Yu Sihua Qi |
| author_sort | Yuanyuan Hou |
| collection | DOAJ |
| description | Background. Propofol is a known intravenous hypnotic drug used for induction and maintenance of sedation and general anesthesia. Emerging studies also reveal a neuroprotective effect of propofol in diverse diseases of neuronal injuries via modulating microglia activation. In this study, we aimed to uncover the downstream targets of propofol in this process. Methods. RNA sequencing analysis to identify genes implicated in the propofol-mediated neuroprotective effect. Quantitative real-time PCR, enzyme-linked immunosorbent assay, and Western blotting analysis were performed to analyze inflammatory gene expression, cytokine levels, and TGM2. BV2 cells and primary microglia were used for functional verification and mechanism studies. Results. The multifunctional enzyme transglutaminase 2 (TGM2) was identified as a putative functional mediator of propofol. TGM2 was significantly upregulated in lipopolysaccharide- (LPS-) primed BV2 cells. Genetic silencing of TGM2 abolished LPS-induced microglial activation. Notably, gain-of-function experiments showed that the proinflammatory effects of TGM2 were dependent on its GTP binding activity instead of transamidase activity. Then, TGM2 was revealed to activate the NF-κB signaling pathway to facilitate microglial activation. Propofol can inhibit TGM2 expression and NF-κB signaling in BV2 cells and primary microglia. Ectopic expression of TGM2 or constitutively active IKKβ (CA-IKKβ) can compromise propofol-induced anti-inflammatory effects. Conclusions. Our findings suggest that TGM2-mediated activation of NF-κB signaling is an important mechanism in the propofol-induced neuroprotective effect that prevents microglial activation. |
| format | Article |
| id | doaj-art-d9763d41fab54cb0956d2afa5e871fac |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-d9763d41fab54cb0956d2afa5e871fac2025-08-20T03:24:17ZengWileyJournal of Immunology Research2314-88612314-71562021-01-01202110.1155/2021/47544544754454Propofol Suppresses Microglia Inflammation by Targeting TGM2/NF-κB SignalingYuanyuan Hou0Xi Xiao1Wei Yu2Sihua Qi3Department of Anesthesiology, The Fourth Affiliated Hospital of the Harbin Medical University, Harbin, 150001 Heilongjiang Province, ChinaDepartment of Anesthesiology, The Fourth Affiliated Hospital of the Harbin Medical University, Harbin, 150001 Heilongjiang Province, ChinaDepartment of Anesthesiology, The Fourth Affiliated Hospital of the Harbin Medical University, Harbin, 150001 Heilongjiang Province, ChinaDepartment of Anesthesiology, The Fourth Affiliated Hospital of the Harbin Medical University, Harbin, 150001 Heilongjiang Province, ChinaBackground. Propofol is a known intravenous hypnotic drug used for induction and maintenance of sedation and general anesthesia. Emerging studies also reveal a neuroprotective effect of propofol in diverse diseases of neuronal injuries via modulating microglia activation. In this study, we aimed to uncover the downstream targets of propofol in this process. Methods. RNA sequencing analysis to identify genes implicated in the propofol-mediated neuroprotective effect. Quantitative real-time PCR, enzyme-linked immunosorbent assay, and Western blotting analysis were performed to analyze inflammatory gene expression, cytokine levels, and TGM2. BV2 cells and primary microglia were used for functional verification and mechanism studies. Results. The multifunctional enzyme transglutaminase 2 (TGM2) was identified as a putative functional mediator of propofol. TGM2 was significantly upregulated in lipopolysaccharide- (LPS-) primed BV2 cells. Genetic silencing of TGM2 abolished LPS-induced microglial activation. Notably, gain-of-function experiments showed that the proinflammatory effects of TGM2 were dependent on its GTP binding activity instead of transamidase activity. Then, TGM2 was revealed to activate the NF-κB signaling pathway to facilitate microglial activation. Propofol can inhibit TGM2 expression and NF-κB signaling in BV2 cells and primary microglia. Ectopic expression of TGM2 or constitutively active IKKβ (CA-IKKβ) can compromise propofol-induced anti-inflammatory effects. Conclusions. Our findings suggest that TGM2-mediated activation of NF-κB signaling is an important mechanism in the propofol-induced neuroprotective effect that prevents microglial activation.http://dx.doi.org/10.1155/2021/4754454 |
| spellingShingle | Yuanyuan Hou Xi Xiao Wei Yu Sihua Qi Propofol Suppresses Microglia Inflammation by Targeting TGM2/NF-κB Signaling Journal of Immunology Research |
| title | Propofol Suppresses Microglia Inflammation by Targeting TGM2/NF-κB Signaling |
| title_full | Propofol Suppresses Microglia Inflammation by Targeting TGM2/NF-κB Signaling |
| title_fullStr | Propofol Suppresses Microglia Inflammation by Targeting TGM2/NF-κB Signaling |
| title_full_unstemmed | Propofol Suppresses Microglia Inflammation by Targeting TGM2/NF-κB Signaling |
| title_short | Propofol Suppresses Microglia Inflammation by Targeting TGM2/NF-κB Signaling |
| title_sort | propofol suppresses microglia inflammation by targeting tgm2 nf κb signaling |
| url | http://dx.doi.org/10.1155/2021/4754454 |
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