Propofol Ameliorates Microglia Activation by Targeting MicroRNA-221/222-IRF2 Axis
Background. Propofol is a widely used intravenous anesthetic drug with potential neuroprotective effect in diverse diseases of neuronal injuries such as traumatic brain injury and ischemic stroke. However, the underlying molecular mechanism remains largely unknown. Methods. Real-time qPCR, enzyme-li...
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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/10.1155/2021/3101146 |
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| _version_ | 1832556901789859840 |
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| author | Xi Xiao Yuanyuan Hou Wei Yu Sihua Qi |
| author_facet | Xi Xiao Yuanyuan Hou Wei Yu Sihua Qi |
| author_sort | Xi Xiao |
| collection | DOAJ |
| description | Background. Propofol is a widely used intravenous anesthetic drug with potential neuroprotective effect in diverse diseases of neuronal injuries such as traumatic brain injury and ischemic stroke. However, the underlying molecular mechanism remains largely unknown. Methods. Real-time qPCR, enzyme-linked immunosorbent assay, and Western blotting were used to identify the expression pattern of miR-221/222, inflammatory genes, cytokines, and IRF2. The biological roles and mechanisms of propofol in microglia activation were determined in BV2 cells and primary microglia. Bioinformatic analysis and luciferase reporter assay were used to confirm the regulatory role of miR-221/222 in Irf2 expression. Results. We found that miR-221 and miR-222 were downstream targets of propofol and were consistently upregulated in lipopolysaccharide- (LPS-) primed BV2 cells. Gain- and loss-of-function studies revealed that miR-221 and miR-222 were profoundly implicated in microglia activation. Then, interferon regulatory factor 2 (Irf2) was identified as a direct target gene of miR-221/222. IRF2 protein levels were reduced by miR-221/222 and increased by propofol treatment. Ectopic expression of IRF2 attenuated the proinflammatory roles induced by LPS in BV2 cells. More importantly, the suppressive effects of propofol on LPS-primed activation of BV2 cells or primary mouse microglia involved the inhibition of miR-221/222-IRF2 axis. Conclusions. Our study highlights the critical function of miR-221/222, which inhibited Irf2 translation, in the anti-inflammatory effects of propofol, and provides a new perspective for the molecular mechanism of propofol-mediated neuroprotective effect. |
| format | Article |
| id | doaj-art-865a429d89304a769ab8c4afee6493c0 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
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| series | Journal of Immunology Research |
| spelling | doaj-art-865a429d89304a769ab8c4afee6493c02025-02-03T05:44:08ZengWileyJournal of Immunology Research2314-88612314-71562021-01-01202110.1155/2021/31011463101146Propofol Ameliorates Microglia Activation by Targeting MicroRNA-221/222-IRF2 AxisXi Xiao0Yuanyuan Hou1Wei 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 widely used intravenous anesthetic drug with potential neuroprotective effect in diverse diseases of neuronal injuries such as traumatic brain injury and ischemic stroke. However, the underlying molecular mechanism remains largely unknown. Methods. Real-time qPCR, enzyme-linked immunosorbent assay, and Western blotting were used to identify the expression pattern of miR-221/222, inflammatory genes, cytokines, and IRF2. The biological roles and mechanisms of propofol in microglia activation were determined in BV2 cells and primary microglia. Bioinformatic analysis and luciferase reporter assay were used to confirm the regulatory role of miR-221/222 in Irf2 expression. Results. We found that miR-221 and miR-222 were downstream targets of propofol and were consistently upregulated in lipopolysaccharide- (LPS-) primed BV2 cells. Gain- and loss-of-function studies revealed that miR-221 and miR-222 were profoundly implicated in microglia activation. Then, interferon regulatory factor 2 (Irf2) was identified as a direct target gene of miR-221/222. IRF2 protein levels were reduced by miR-221/222 and increased by propofol treatment. Ectopic expression of IRF2 attenuated the proinflammatory roles induced by LPS in BV2 cells. More importantly, the suppressive effects of propofol on LPS-primed activation of BV2 cells or primary mouse microglia involved the inhibition of miR-221/222-IRF2 axis. Conclusions. Our study highlights the critical function of miR-221/222, which inhibited Irf2 translation, in the anti-inflammatory effects of propofol, and provides a new perspective for the molecular mechanism of propofol-mediated neuroprotective effect.http://dx.doi.org/10.1155/2021/3101146 |
| spellingShingle | Xi Xiao Yuanyuan Hou Wei Yu Sihua Qi Propofol Ameliorates Microglia Activation by Targeting MicroRNA-221/222-IRF2 Axis Journal of Immunology Research |
| title | Propofol Ameliorates Microglia Activation by Targeting MicroRNA-221/222-IRF2 Axis |
| title_full | Propofol Ameliorates Microglia Activation by Targeting MicroRNA-221/222-IRF2 Axis |
| title_fullStr | Propofol Ameliorates Microglia Activation by Targeting MicroRNA-221/222-IRF2 Axis |
| title_full_unstemmed | Propofol Ameliorates Microglia Activation by Targeting MicroRNA-221/222-IRF2 Axis |
| title_short | Propofol Ameliorates Microglia Activation by Targeting MicroRNA-221/222-IRF2 Axis |
| title_sort | propofol ameliorates microglia activation by targeting microrna 221 222 irf2 axis |
| url | http://dx.doi.org/10.1155/2021/3101146 |
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