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Fluoxetine suppresses inflammatory reaction in microglia under OGD/R challenge via modulation of NF-?B signaling.

ABSTRACT: We aimed to investigate the anti-inflammatory role of fluoxetine, a selective serotonin reuptake inhibitor, in microglia (MG) and the mechanisms under oxygen glucose deprivation/reoxygenation (OGD/R). An OGD/R model on BV-2 cells was used for the study of microglia under ischemia/reperfusion injury in ischemic stroke. Lentiviral transfection was applied to knock down I?B-?. Enzyme-linked immunosorbent assay (ELISA) was used for detecting levels of TNF-?, IL-1?, and IL-6, and real-time PCR was used to assess the expression of I?B-? protein. Western blotting was applied to analyze NF-?B-signaling related proteins and Cell Counting Kit-8 (CCK-8) was used for assessing cell viability. Molecular docking and drug affinity responsive target stability (DARTS) assay were used for the detection of the interaction between I?B-? and fluoxetine. We found that fluoxetine decreased the levels of TNF-?, IL-1?, and IL-6 in supernatant as well as NF-?B subunits p65 and p50 in BV-2 cells under OGD/R. Fluoxetine significantly increased the level of I?B-? through the inhibition of I?B-? ubiquitylation and promoted the bonding of I?B-? and fluoxetine in BV-2 cells under OGD/R. Knocking down I?B-? attenuated the decreasing effect of TNF-?, IL-1?, and IL-6 as well as p65 and p50 in BV-2 cells under OGD/R led to by fluoxetine. In conclusion, our present study demonstrated the anti-inflammatory role of fluoxetine and its mechanisms related to the modulation of NF-?B-related signaling in MG under ischemia/reperfusion challenge.

SUBMITTER: Tian M

PROVIDER: S-EPMC6487262 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Fluoxetine suppresses inflammatory reaction in microglia under OGD/R challenge via modulation of NF-κB signaling.

Tian Mouli M Yang Mei M Li Zhenjie Z Wang Yiru Y Chen Wei W Yang Liye L Li Yonghua Y Yuan Hongbin H

Bioscience reports 20190426 4

We aimed to investigate the anti-inflammatory role of fluoxetine, a selective serotonin reuptake inhibitor, in microglia (MG) and the mechanisms under oxygen glucose deprivation/reoxygenation (OGD/R). An OGD/R model on BV-2 cells was used for the study of microglia under ischemia/reperfusion injury in ischemic stroke. Lentiviral transfection was applied to knock down IκB-α. Enzyme-linked immunosorbent assay (ELISA) was used for detecting levels of TNF-α, IL-1β, and IL-6, and real-time PCR was us ...[more]

PMID: 30944203

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Fluoxetine suppresses inflammatory reaction in microglia under OGD/R challenge via modulation of NF-?B signaling.

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Fluoxetine suppresses inflammatory reaction in microglia under OGD/R challenge via modulation of NF-κB signaling.

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