https://doi.org/10.4081/ejh.2024.4034
Propofol alleviates M1 polarization and neuroinflammation of microglia in a subarachnoid hemorrhage model in vitro, by targeting the miR-140-5p/TREM-1/NF-κB signaling axis
Submitted: 2 April 2024
Accepted: 9 August 2024
Published: 17 September 2024
Accepted: 9 August 2024
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
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Subarachnoid hemorrhage (SAH) is a devastating stroke caused by ruptured intracranial aneurysms, leading to blood accumulation around the brain. Early brain injury (EBI) within 72 h post-SAH worsens prognosis, primarily due to intense neuroinflammation. Microglia, pivotal in central nervous system defense and repair, undergo M1 to M2 polarization post-SAH, with M1 exacerbating neuroinflammation. Propofol (PPF), an anesthetic with anti-inflammatory properties, shows promise in mitigating neuroinflammation in SAH by modulating microglial activation. It likely acts through microRNAs like miR-140-5p, which attenuates microglial activation and inflammation by targeting TREM-1 and the NF-κB pathway. Understanding these mechanisms could lead to new therapeutic approaches for SAH-related EBI. In this study, BV-2 cell was used to establish in vitro model of SAH, and the expression of miR-140-5p and TREM-1 was detected after modeling. Microglial activity, apoptosis, the inflammatory pathway and response, oxidative damage, and M1/M2 polarization of microglia were evaluated by drug administration or transfection according to experimental groups. Finally, the targeting relationship between miR-140-5p and TREM-1 was verified by dual luciferase reporter assays, and the effect of PPF on the miR-140-5p/TREM-1/NF-κB signaling cascade was evaluated by RT‒qPCR or Western blotting. PPF effectively mitigates apoptosis, neuroinflammation, oxidative damage, and M1 microglial polarization in SAH. In SAH cells, PPF upregulates miR-140-5p and downregulates TREM-1. Mechanistically, PPF boosts miR-140-5p expression, while TREM-1, a downstream target of miR-140-5p, inhibits NF-κB signaling by regulating TREM-1, promoting M1 to M2 microglial polarization. Reduced miR-140-5p or increased TREM-1 counters PPF's therapeutic impact on SAH cells. In conclusion, PPF plays a neuroprotective role in SAH by regulating the miR-140-5p/TREM-1/NF-κB signaling axis to inhibit neuroinflammation and M1 polarization of microglia.
Neifert SN, Chapman EK, Martini ML, Shuman WH, Schupper AJ, Oermann EK, et al. Aneurysmal subarachnoid hemorrhage: the last decade. Transl Stroke Res 2021;12:428-46.
DOI: https://doi.org/10.1007/s12975-020-00867-0
Rass V, Helbok R. Early brain injury after poor-grade subarachnoid hemorrhage. Curr Neurol Neurosci 2019;19:78.
DOI: https://doi.org/10.1007/s11910-019-0990-3
Leclerc JL, Garcia JM, Diller MA, Carpenter AM, Kamat PK, Hoh BL, et al. A Comparison of pathophysiology in humans and rodent models of subarachnoid hemorrhage. Front Mol Neurosci 2018;11:71.
DOI: https://doi.org/10.3389/fnmol.2018.00071
Heinz R, Brandenburg S, Nieminen-Kelha M, Kremenetskaia I, Boehm-Sturm P, Vajkoczy P, et al. Microglia as target for anti-inflammatory approaches to prevent secondary brain injury after subarachnoid hemorrhage (SAH). J Neuroinflamm 2021;18:36.
DOI: https://doi.org/10.1186/s12974-021-02085-3
Salter MW, Stevens B. Microglia emerge as central players in brain disease. Nat Med 2017;23:1018-27.
DOI: https://doi.org/10.1038/nm.4397
Karthikeyan A, Patnala R, Jadhav SP, Eng-Ang L, Dheen ST. MicroRNAs: key players in microglia and astrocyte mediated inflammation in CNS pathologies. Curr Med Chem 2016;23:3528-46.
DOI: https://doi.org/10.2174/0929867323666160814001040
Tsai TH, Chang CH, Lin SH, Su YF, Tsai YC, Yang SF, et al. Therapeutic effect of and mechanisms underlying the effect of miR-195-5p on subarachnoid hemorrhage-induced vasospasm and brain injury in rats. Peerj 2021;9:e11395.
DOI: https://doi.org/10.7717/peerj.11395
Zhou R, Yang Z, Tang X, Tan Y, Wu X, Liu F. Propofol protects against focal cerebral ischemia via inhibition of microglia-mediated proinflammatory cytokines in a rat model of experimental stroke. Plos One 2013;8:e82729.
DOI: https://doi.org/10.1371/journal.pone.0082729
Hou Y, Xiao X, Yu W, Qi S. Propofol suppresses microglia inflammation by targeting TGM2/NF-kappaB signaling. J Immunol Res 2021;2021:4754454.
DOI: https://doi.org/10.1155/2021/4754454
Xiao X, Hou Y, Yu W, Qi S. Propofol ameliorates microglia activation by targeting microRNA-221/222-IRF2 axis. J Immunol Res 2021;2021:3101146.
DOI: https://doi.org/10.1155/2021/3101146
Shi SS, Zhang HB, Wang CH, Yang WZ, Liang RS, Chen Y, et al. Propofol attenuates early brain injury after subarachnoid hemorrhage in rats. J Mol Neurosci 2015;57:538-45.
DOI: https://doi.org/10.1007/s12031-015-0634-2
Zhang HB, Tu XK, Chen Q, Shi SS. Propofol reduces inflammatory brain injury after subarachnoid hemorrhage: involvement of PI3K/Akt pathway. J Stroke Cerebrovasc 2019;28:104375.
DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2019.104375
Zheng X, Huang H, Liu J, Li M, Liu M, Luo T. propofol attenuates inflammatory response in LPS-activated microglia by regulating the miR-155/SOCS1 pathway. Inflammation 2018;41:11-9.
DOI: https://doi.org/10.1007/s10753-017-0658-6
Wang S, Cui Y, Xu J, Gao H. miR-140-5p attenuates neuroinflammation and brain injury in rats following intracerebral hemorrhage by targeting TLR4. Inflammation 2019;42:1869-77.
DOI: https://doi.org/10.1007/s10753-019-01049-3
Song W, Wang T, Shi B, Wu Z, Wang W, Yang Y. Neuroprotective effects of microRNA-140-5p on ischemic stroke in mice via regulation of the TLR4/NF-kappaB axis. Brain Res Bull 2021;168:8-16.
DOI: https://doi.org/10.1016/j.brainresbull.2020.10.020
Wang P, Dong S, Liu F, Liu A, Wang Z. MicroRNA-140-5p shuttled by microglia-derived extracellular vesicles attenuates subarachnoid hemorrhage-induced microglia activation and inflammatory response via MMD downregulation. Exp Neurol 2023;359:114265.
DOI: https://doi.org/10.1016/j.expneurol.2022.114265
Wang P, Xue Y, Zuo Y, Xue Y, Zhang JH, Duan J, et al. Exosome-encapsulated microRNA-140-5p alleviates neuronal injury following subarachnoid hemorrhage by regulating IGFBP5-mediated PI3K/AKT signaling pathway. Mol Neurobiol 2022;59:7212-28.
DOI: https://doi.org/10.1007/s12035-022-03007-x
Sun XG, Ma Q, Jing G, Wang L, Hao XD, Wang GQ. Early elevated levels of soluble triggering receptor expressed on myeloid cells-1 in subarachnoid hemorrhage patients. Neurol Sci 2017;38:873-7.
DOI: https://doi.org/10.1007/s10072-017-2853-5
Sun XG, Ma Q, Jing G, Wang GQ, Hao XD, Wang L. Increased levels of soluble triggering receptor expressed on myeloid cells-1 in cerebrospinal fluid of subarachnoid hemorrhage patients. J Clin Neurosci 2017;35:139-43.
DOI: https://doi.org/10.1016/j.jocn.2016.09.005
Sharif O, Knapp S. From expression to signaling: roles of TREM-1 and TREM-2 in innate immunity and bacterial infection. Immunobiology 2008;213:701-13.
DOI: https://doi.org/10.1016/j.imbio.2008.07.008
Pang J, Peng J, Matei N, Yang P, Kuai L, Wu Y, et al. Apolipoprotein E exerts a whole-brain protective property by promoting M1? Microglia quiescence after experimental subarachnoid hemorrhage in mice. Transl Stroke Res 2018;9:654-68.
DOI: https://doi.org/10.1007/s12975-018-0665-4
Gao Y, Zhuang Z, Lu Y, Tao T, Zhou Y, Liu G, et al. Curcumin mitigates neuro-inflammation by modulating microglia polarization through inhibiting TLR4 axis signaling pathway following experimental subarachnoid hemorrhage. Front Neurosci 2019;13:1223.
DOI: https://doi.org/10.3389/fnins.2019.01223
Chen J, Zheng ZV, Lu G, Chan WY, Zhang Y, Wong G. Microglia activation, classification and microglia-mediated neuroinflammatory modulators in subarachnoid hemorrhage. Neural Regen Res 2022;17:1404-11.
DOI: https://doi.org/10.4103/1673-5374.330589
Liu H, Guo D, Wang J, Zhang W, Zhu Z, Zhu K, et al. Aloe-emodin from Sanhua decoction inhibits neuroinflammation by regulating microglia polarization after subarachnoid hemorrhage. J Ethnopharmacol 2024;322:117583.
DOI: https://doi.org/10.1016/j.jep.2023.117583
Xia DY, Yuan JL, Jiang XC, Qi M, Lai NS, Wu LY, et al. SIRT1 promotes M2 microglia polarization via reducing ROS-mediated NLRP3 inflammasome signaling after subarachnoid hemorrhage. Front Immunol 2021;12:770744.
DOI: https://doi.org/10.3389/fimmu.2021.770744
Tian Y, Liu B, Li Y, Zhang Y, Shao J, Wu P, et al. Activation of RARalpha receptor attenuates neuroinflammation after SAH via promoting M1-to-M2 phenotypic polarization of microglia and regulating Mafb/Msr1/PI3K-Akt/NF-kappaB pathway. Front Immunol 2022;13:839796.
DOI: https://doi.org/10.3389/fimmu.2022.839796
Wei J, Li T, Lin S, Zhang B, Li X. Dihydrotestosterone reduces neuroinflammation in spinal cord injury through NF-kappaB and MAPK pathway. Cell Mol Biol 2024;70:213-8.
DOI: https://doi.org/10.14715/cmb/2024.70.1.29
Wu Y, Yang D. Effects of bacterial biofilm on regulation of neurovascular unit functions and neuroinflammation of patients with ischemic cerebral stroke by immunocyte. Cell Mol Biol 2023;69:81-6.
DOI: https://doi.org/10.14715/cmb/2022.69.1.14
Li B, Liang C, Lv Y, Tan Y, Chen W. MiR-22 inhibits myocardial fibrosis in rats with myocardial infarction by targeting PTEN/Akt/mTOR signaling pathway. Cell Mol Biol 2024;70:28-33.
DOI: https://doi.org/10.14715/cmb/2024.70.1.4
Ma Z, Li K, Chen P, Pan J, Li X, Zhao G. Propofol attenuates inflammatory damage via inhibiting NLRP1-Casp1-Casp6 signaling in ischemic brain injury. Biol Pharm Bull 2020;43:1481-9.
DOI: https://doi.org/10.1248/bpb.b20-00050
Yuan J, Cui G, Li W, Zhang X, Wang X, Zheng H, et al. Propofol enhances hemoglobin-induced cytotoxicity in neurons. Anesth Analg 2016;122:1024-30.
DOI: https://doi.org/10.1213/ANE.0000000000001123
Wang X, Yang X, Han F, Gao L, Zhou Y. Propofol improves brain injury induced by chronic cerebral hypoperfusion in rats. Food Sci Nutr 2021;9:2801-9.
DOI: https://doi.org/10.1002/fsn3.1915
Yu H, Wang X, Kang F, Chen Z, Meng Y, Dai M. Propofol attenuates inflammatory damage on neurons following cerebral infarction by inhibiting excessive activation of microglia. Int J Mol Med 2019;43:452-60.
DOI: https://doi.org/10.3892/ijmm.2018.3974
Zhang F, Wang Z, Sun B, Huang Y, Chen C, Hu J, et al. Propofol rescued astrocytes from LPS-induced inflammatory response via blocking LncRNA-MEG3/NF-κB axis. Curr Neurovasc Res 2022;19:5-18.
DOI: https://doi.org/10.2174/1567202619666220316112509
Syed NS, Kamarudin AA, Abdul SS, Norrrahim M, Abdul LN, Wah L. The linkage between microRNA and cancer and its delivery as cancer therapy: a mini-review. Cell Mol Biol 2023;69:7-18.
DOI: https://doi.org/10.14715/cmb/2023.69.7.2
Lai NS, Zhang JQ, Qin FY, Sheng B, Fang XG, Li ZB. Serum microRNAs are non-invasive biomarkers for the presence and progression of subarachnoid haemorrhage. Bioscience Rep 2017;37:BSR20160480.
DOI: https://doi.org/10.1042/BSR20160480
Akdeniz FT, Barut Z. Analysis of miRNA-199-5p expression levels in serum samples of patients with lumbar disc degeneration. Cell Mol Biol 2023;69:83-7.
DOI: https://doi.org/10.14715/cmb/2023.69.12.14
Geng Y, Chen P, Zhang L, Li X, Song C, Wei X et al. LncRNA MALAT1 regulates growth of carcinoma of the lung through modulating miR-338-3p/PYCR2 axis. Cell Mol Biol 2023;69:133-40.
DOI: https://doi.org/10.14715/cmb/2023.69.4.21
Yu K, Xu R, Wu L, Li W, Lin R, Dai M, et al. Effects of microRNA-320 on learning and memory in mice with vascular cognitive impairment caused via cerebral ischemia. Cell Mol Biol 2023;69:112-9.
DOI: https://doi.org/10.14715/cmb/2023.69.13.18
Dai N, Ma H, Feng Y. Silencing of long non-coding RNA SDCBP2-AS1/microRNA-656-3p/CRIM1 axis promotes ferroptosis of lung cancer cells. Cell Mol Biol 2023;69:189-94.
DOI: https://doi.org/10.14715/cmb/2023.69.9.29
Tang Y, Zhang X, Wang S, Liu L, Wang Q, Liu Y, et al. Up-regulation of lncRNA WT1-AS ameliorates Abeta-stimulated neuronal injury through modulation of miR-186-5p/CCND2 axis in Alzheimer's disease. Cell Mol Biol 2024;70:200-6.
DOI: https://doi.org/10.14715/cmb/2024.70.1.27
Bi L, Zhou Y, Zhang Y, Zhang X. MiR-27a-3p exacerbates cell migration and invasion in right-sided/left-sided colorectal cancer by targeting TGFBR2/TCF7L2. Cell Mol Biol 2024;70:148-54.
DOI: https://doi.org/10.14715/cmb/2024.70.1.20
Yu H, Tu S, Shen C, Bai X, Sun J, Shi M, et al. Effects of the lncRNA MALAT1 gene region rs664589 site mutation on acute myocardial infarction in Chinese Han. Cell Mol Biol 2024;70:119-27.
DOI: https://doi.org/10.14715/cmb/2024.70.1.16
Wang WX, Springer JE, Hatton KW. MicroRNAs as biomarkers for predicting complications following aneurysmal subarachnoid hemorrhage. Int J Mol Sci 2021;22:9492.
DOI: https://doi.org/10.3390/ijms22179492
Jafri I. MiRNA a new insight in metabolic and human diseases: a review. Cell Mol Biol 2023;69:102-10.
DOI: https://doi.org/10.14715/cmb/2023.69.8.16
Zhu F, Li Q, Yang Y, Wang L, Wang J. Propofol suppresses proliferation, migration, invasion and promotes apoptosis by upregulating microRNA-140-5p in gastric cancer cells. Oncotargets Ther 2019;12:10129-38.
DOI: https://doi.org/10.2147/OTT.S225360
Makowska M, Smolarz B, Romanowicz H. microRNAs in subarachnoid hemorrhage (review of literature). J Clin Med 2022;11:4630.
DOI: https://doi.org/10.3390/jcm11154630
Sun XG, Duan H, Jing G, Wang G, Hou Y, Zhang M. Inhibition of TREM-1 attenuates early brain injury after subarachnoid hemorrhage via downregulation of p38MAPK/MMP-9 and preservation of ZO-1. Neuroscience 2019;406:369-75.
DOI: https://doi.org/10.1016/j.neuroscience.2019.03.032
Jin J, Duan J, Du L, Xing W, Peng X, Zhao Q. Inflammation and immune cell abnormalities in intracranial aneurysm subarachnoid hemorrhage (SAH): Relevant signaling pathways and therapeutic strategies. Front Immunol 2022;13:1027756.
DOI: https://doi.org/10.3389/fimmu.2022.1027756
How to Cite
Wang, L., Fan, Z., Wang, H., & Xiang, S. (2024). Propofol alleviates M1 polarization and neuroinflammation of microglia in a subarachnoid hemorrhage model <i>in vitro</i>, by targeting the miR-140-5p/TREM-1/NF-κB signaling axis. European Journal of Histochemistry, 68(3). https://doi.org/10.4081/ejh.2024.4034
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