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Updated: May 28, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
miR-155 modulates microglia-mediated immune response by down-regulating SOCS-1 and promoting cytokine and nitric
Ana L Cardoso1, Joana R Guedes, Luís Pereira de Almeida
1Centre for Neuroscience and Cell Biology, University of Coimbra, Portugal. alcardoso@ci.uc.pt
Abstract:
Innate immunity constitutes the first line of defence against both external and endogenous threats in the brain, and microglia cells are considered key mediators of this process. Recent studies have shown that microRNAs (miRNAs) may play a determinant role in the regulation of gene expression during innate immune responses. The major goal of this work was to investigate the contribution of a specific miRNA - miR-155 - to the modulation of the microglia-mediated immune response. For this purpose, in vitro studies were performed in N9 microglia cells to evaluate changes in the levels of this miRNA following microglia activation. A strong up-regulation of miR-155 expression was observed following microglia exposure to lipopolysaccharide, which was consistent with a decrease in the levels of the suppressor of cytokine signalling 1 (SOCS-1) protein, a key inhibitor of the inflammatory process and a predicted target of miR-155. The miR-155 knockdown by anti-miRNA oligonucleotides up-regulated SOCS-1 mRNA and protein levels and significantly decreased the production of nitric oxide and the expression of inflammatory cytokines and inducible nitric oxide synthase. Finally, treatment of neuronal primary cultures with conditioned medium obtained from microglia cells, in which miR-155 was inhibited before cell activation, decreased inflammatory-mediated neuronal cell death. Overall, our results show that miR-155 has a pro-inflammatory role in microglia and is necessary for the progression of the immune response through the modulation of SOCS-1, suggesting that, in a chronic inflammatory context, miR-155 inhibition can have a neuroprotective effect.
Insights
MicroRNA-155 (miR-155) promotes brain inflammation by inhibiting SOCS-1 in microglia. Inhibiting miR-155 reduces inflammation and protects neurons, suggesting a therapeutic target for neurodegenerative diseases.
Area of Science:
- Neuroimmunology
- Molecular Biology
Background:
- Microglia are key immune cells in the brain, mediating innate immunity.
- MicroRNAs (miRNAs) regulate gene expression during immune responses.
- miR-155's role in microglia-mediated immunity requires further investigation.
Purpose of the Study:
- To investigate the role of miR-155 in microglia-mediated immune responses.
- To determine if miR-155 modulates the inflammatory response via SOCS-1.
- To assess the neuroprotective potential of inhibiting miR-155.
Main Methods:
- In vitro studies using N9 microglia cells and primary neuronal cultures.
- Microglia activation using lipopolysaccharide (LPS).
- Quantification of miR-155, SOCS-1 mRNA and protein, nitric oxide, and inflammatory cytokines.
- miR-155 knockdown using anti-miRNA oligonucleotides.
Main Results:
- LPS exposure significantly upregulated miR-155 in microglia.
- miR-155 upregulation correlated with decreased SOCS-1 protein levels.
- miR-155 knockdown increased SOCS-1, reduced nitric oxide and inflammatory cytokine production.
- Inhibition of miR-155 in microglia conditioned medium reduced neuronal cell death.
Conclusions:
- miR-155 plays a pro-inflammatory role in microglia by suppressing SOCS-1.
- miR-155 is essential for the progression of the neuroinflammatory response.
- Inhibition of miR-155 demonstrates neuroprotective effects in an inflammatory context.
