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Detection of MicroRNAs in Microglia by Real-time PCR in Normal CNS and During Neuroinflammation
Published on: July 23, 2012
Melatonin Alters the miRNA Transcriptome of Inflammasome Activation in Murine Microglial Cells
Emre Tarakcioglu1,2, Bora Tastan1,2, Burak I Arioz1,2
1Izmir Biomedicine and Genome Center, 35340, Izmir, Balcova, Turkey.
Abstract:
Systemic inflammation can have devastating effects on the central nervous system via its resident immune cells, the microglia. One of the primary mediators of this inflammation is inflammasomes, multiprotein complexes that trigger a release of inflammatory proteins when activated. Melatonin, a hormone with anti-inflammatory effects, is an attractive candidate for suppressing such inflammation. In this study, we have investigated how melatonin alters the microRNA (miRNA) transcriptome of microglial cells. For that purpose, we have performed RNA sequencing on a lipopolysaccharide and adenosine triphosphate (LPS + ATP) induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation model in the N9 mouse microglial cell line, with and without melatonin pre-treatment. We have identified 136 differentially expressed miRNAs in cells exposed to LPS + ATP compared to controls and 10 differentially expressed miRNAs in melatonin pre-treated cells compared to the inflammasome group. We have identified miR-155-3p as a miRNA that is upregulated with inflammasome activation and downregulated with melatonin treatment. We further confirmed this pattern of miR-155-3p expression in the brains of mice injected intraperitoneally with LPS. Moreover, an overexpression study with miRNA-155-3p mimic supported the idea that the protective effects of melatonin in NLRP3 inflammasome activation are partly associated with miRNA-155-3p inhibition.
Insights
Melatonin, an anti-inflammatory hormone, suppresses microglial inflammasome activation by altering microRNA (miRNA) expression. It downregulates miR-155-3p, a key mediator of this inflammatory response, offering neuroprotective benefits.
Area of Science:
- Neuroimmunology
- Molecular Biology
- Pharmacology
Background:
- Systemic inflammation impacts the central nervous system through microglia activation.
- Inflammasomes, like NLRP3, are key mediators of microglial inflammatory responses.
- Melatonin possesses anti-inflammatory properties, making it a potential therapeutic agent.
Purpose of the Study:
- To investigate the effect of melatonin on the microRNA (miRNA) transcriptome in microglial cells during inflammasome activation.
- To identify specific miRNAs regulated by melatonin in the context of NLRP3 inflammasome activation.
Main Methods:
- Utilized a lipopolysaccharide and adenosine triphosphate (LPS+ATP) induced NLRP3 inflammasome activation model in the N9 mouse microglial cell line.
- Performed RNA sequencing to analyze miRNA expression profiles with and without melatonin pre-treatment.
- Confirmed miR-155-3p expression changes in vivo using LPS-injected mouse brains.
Main Results:
- Identified 136 differentially expressed miRNAs upon LPS+ATP stimulation.
- Observed 10 differentially expressed miRNAs in melatonin pre-treated cells compared to the inflammasome group.
- Found miR-155-3p to be upregulated during inflammasome activation and downregulated by melatonin treatment.
- Demonstrated that melatonin's protective effects against NLRP3 inflammasome activation are partly mediated by inhibiting miR-155-3p.
Conclusions:
- Melatonin modulates the miRNA transcriptome in activated microglia.
- miR-155-3p is a key regulator of NLRP3 inflammasome activation and is targeted by melatonin.
- Melatonin's neuroprotective effects in inflammasome-mediated inflammation involve the downregulation of miR-155-3p.
