Zileuton, a 5-Lipoxygenase Inhibitor, Attenuates Haemolysate-Induced BV-2 Cell Activation by Suppressing the MyD88/NF-κB Pathway
M1 microglia induce neuroinflammation-related neuronal death in animal models of spontaneous subarachnoid haemorrhage. Zileuton is a 5-lipoxygenase inhibitor that reduces the levels of downstream pro-inflammatory cytokines. This study aimed to investigate whether zileuton inhibits microglial activat...
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MDPI AG
2022-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/9/4910 |
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| author | Hui-Yuan Su Yi-Cheng Tsai Hung-Pei Tsai Chih-Lung Lin |
| author_facet | Hui-Yuan Su Yi-Cheng Tsai Hung-Pei Tsai Chih-Lung Lin |
| author_sort | Hui-Yuan Su |
| collection | DOAJ |
| description | M1 microglia induce neuroinflammation-related neuronal death in animal models of spontaneous subarachnoid haemorrhage. Zileuton is a 5-lipoxygenase inhibitor that reduces the levels of downstream pro-inflammatory cytokines. This study aimed to investigate whether zileuton inhibits microglial activation and describe its underlying mechanisms. BV-2 cells were exposed to 1 mg/mL haemolysate for 30 min, followed by treatment with different concentrations (5, 10, 15, or 20 μM) of zileuton for 24 h. The cells were then assessed for viability, polarisation, and protein expression levels. Haemolysate increases the viability of BV-2 cells and induces M1 polarisation. Subsequent exposure to high concentrations of zileuton decreased the viability of BV-2 cells, shifted the polarisation to the M2 phenotype, suppressed the expression of 5-lipoxygenase, decreased tumour necrosis factor α levels, and increased interleukin-10 levels. Furthermore, high concentrations of zileuton suppressed the expression of myeloid differentiation primary response protein 88 and reduced the phosphorylated-nuclear factor-kappa B (NF-kB)/NF-kB ratio. Therefore, phenotype reversal from M1 to M2 is a possible mechanism by which zileuton attenuates haemolysate-induced neuroinflammation after spontaneous subarachnoid haemorrhage. |
| first_indexed | 2024-03-10T04:05:27Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:05:27Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-80a76434328f4c8eb9eba4d3898683942023-11-23T08:24:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01239491010.3390/ijms23094910Zileuton, a 5-Lipoxygenase Inhibitor, Attenuates Haemolysate-Induced BV-2 Cell Activation by Suppressing the MyD88/NF-κB PathwayHui-Yuan Su0Yi-Cheng Tsai1Hung-Pei Tsai2Chih-Lung Lin3Department of Surgery, Division of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung 807, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, TaiwanDepartment of Surgery, Division of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung 807, TaiwanDepartment of Surgery, Division of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung 807, TaiwanM1 microglia induce neuroinflammation-related neuronal death in animal models of spontaneous subarachnoid haemorrhage. Zileuton is a 5-lipoxygenase inhibitor that reduces the levels of downstream pro-inflammatory cytokines. This study aimed to investigate whether zileuton inhibits microglial activation and describe its underlying mechanisms. BV-2 cells were exposed to 1 mg/mL haemolysate for 30 min, followed by treatment with different concentrations (5, 10, 15, or 20 μM) of zileuton for 24 h. The cells were then assessed for viability, polarisation, and protein expression levels. Haemolysate increases the viability of BV-2 cells and induces M1 polarisation. Subsequent exposure to high concentrations of zileuton decreased the viability of BV-2 cells, shifted the polarisation to the M2 phenotype, suppressed the expression of 5-lipoxygenase, decreased tumour necrosis factor α levels, and increased interleukin-10 levels. Furthermore, high concentrations of zileuton suppressed the expression of myeloid differentiation primary response protein 88 and reduced the phosphorylated-nuclear factor-kappa B (NF-kB)/NF-kB ratio. Therefore, phenotype reversal from M1 to M2 is a possible mechanism by which zileuton attenuates haemolysate-induced neuroinflammation after spontaneous subarachnoid haemorrhage.https://www.mdpi.com/1422-0067/23/9/49105-lipoxygenaseBV-2 cellsmicrogliasubarachnoid haemorrhagezileuton |
| spellingShingle | Hui-Yuan Su Yi-Cheng Tsai Hung-Pei Tsai Chih-Lung Lin Zileuton, a 5-Lipoxygenase Inhibitor, Attenuates Haemolysate-Induced BV-2 Cell Activation by Suppressing the MyD88/NF-κB Pathway International Journal of Molecular Sciences 5-lipoxygenase BV-2 cells microglia subarachnoid haemorrhage zileuton |
| title | Zileuton, a 5-Lipoxygenase Inhibitor, Attenuates Haemolysate-Induced BV-2 Cell Activation by Suppressing the MyD88/NF-κB Pathway |
| title_full | Zileuton, a 5-Lipoxygenase Inhibitor, Attenuates Haemolysate-Induced BV-2 Cell Activation by Suppressing the MyD88/NF-κB Pathway |
| title_fullStr | Zileuton, a 5-Lipoxygenase Inhibitor, Attenuates Haemolysate-Induced BV-2 Cell Activation by Suppressing the MyD88/NF-κB Pathway |
| title_full_unstemmed | Zileuton, a 5-Lipoxygenase Inhibitor, Attenuates Haemolysate-Induced BV-2 Cell Activation by Suppressing the MyD88/NF-κB Pathway |
| title_short | Zileuton, a 5-Lipoxygenase Inhibitor, Attenuates Haemolysate-Induced BV-2 Cell Activation by Suppressing the MyD88/NF-κB Pathway |
| title_sort | zileuton a 5 lipoxygenase inhibitor attenuates haemolysate induced bv 2 cell activation by suppressing the myd88 nf κb pathway |
| topic | 5-lipoxygenase BV-2 cells microglia subarachnoid haemorrhage zileuton |
| url | https://www.mdpi.com/1422-0067/23/9/4910 |
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