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Anti-inflammatory effects of fluoxetine in lipopolysaccharide(LPS)-stimulated microglial cells
Dexiang Liu1, Zhen Wang, Shangming Liu
1Institute of Medical Psychology, Shandong University School of Medicine, Jinan, Shandong, PR China.
Abstract:
Recent evidence has suggested that microglial activation plays an important role in the pathogenesis of depression. Activated microglia can secrete various pro-inflammatory cytokines and neurotoxic mediators, which may contribute to the development and maintenance of depression. Thus, inhibition of microglial activation may have a therapeutic benefit in the treatment of depression. In the present study, using BV2 microglial cell line and primary microglial culture, we investigated if fluoxetine, the most widely used antidepressant, can inhibit microglia activation. Our results showed that fluoxetine significantly inhibited lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-α), interleukin- 6 (IL-6) and nitric oxide (NO). By RT-PCR, the mRNA level of these pro-inflammatory cytokines and iNOS was also attenuated by fluoxetine. We further investigated the intracellular signaling mechanism regulating the production of pro-inflammatory cytokines and NO from LPS-activated microglia. The results showed that fluoxetine inhibited IκB-a degradation, phosphorylation and nuclear translocation of the p65 subunit of NF-κB, and phosphorylation of p38 mitogen-activated protein kinase (MAPK) in the LPS-stimulated microglia. Taken together, our results suggest that the therapeutic effects of fluoxetine are partially mediated by modulating microglial activation.
Insights
Fluoxetine, a common antidepressant, was found to inhibit microglial activation, a key factor in depression pathogenesis. This suggests a new therapeutic mechanism for fluoxetine involving the modulation of neuroinflammation.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Microglial activation is implicated in depression pathogenesis.
- Activated microglia release pro-inflammatory cytokines and neurotoxic mediators, contributing to depression.
Purpose of the Study:
- To investigate if fluoxetine inhibits microglial activation.
- To explore the underlying signaling pathways affected by fluoxetine in microglia.
Main Methods:
- Utilized BV2 microglial cell line and primary microglial cultures.
- Assessed the effects of fluoxetine on lipopolysaccharide (LPS)-induced cytokine and nitric oxide production.
- Analyzed mRNA levels of pro-inflammatory mediators using RT-PCR.
- Investigated intracellular signaling pathways including NF-κB and MAPK.
Main Results:
- Fluoxetine significantly inhibited LPS-induced production of TNF-α, IL-6, and NO.
- Fluoxetine reduced the mRNA levels of these pro-inflammatory mediators and iNOS.
- Fluoxetine suppressed IκB-a degradation, NF-κB p65 nuclear translocation, and p38 MAPK phosphorylation in LPS-stimulated microglia.
Conclusions:
- Fluoxetine exhibits inhibitory effects on microglial activation.
- The therapeutic benefits of fluoxetine may be partly attributed to its modulation of microglial activation and neuroinflammation.
