miR‐155 modulates microglia‐mediated immune response by down‐regulating SOCS‐1 and promoting cytokine and nitric oxide production
Open Access
- 4 October 2011
- journal article
- research article
- Published by Wiley in Immunology
- Vol. 135 (1), 73-88
- https://doi.org/10.1111/j.1365-2567.2011.03514.x
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.Keywords
This publication has 33 references indexed in Scilit:
- Interleukin 4 induces the apoptosis of mouse microglial cells by a caspase-dependent mechanismNeurobiology of Disease, 2011
- Inflammatory cytokines regulate microRNA-155 expression in human retinal pigment epithelial cells by activating JAK/STAT pathwayBiochemical and Biophysical Research Communications, 2010
- SOCS1 and SOCS3 in the control of CNS immunityTrends in Immunology, 2009
- miR-155 gene: A typical multifunctional microRNABiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2009
- Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritisArthritis & Rheumatism, 2008
- Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor developmentProceedings of the National Academy of Sciences of the United States of America, 2007
- Microglial activation as a priming event leading to paraquat-induced dopaminergic cell degenerationNeurobiology of Disease, 2007
- MicroRNA-155 is induced during the macrophage inflammatory responseProceedings of the National Academy of Sciences of the United States of America, 2007
- NF-κB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responsesProceedings of the National Academy of Sciences of the United States of America, 2006
- BIC and miR‐155 are highly expressed in Hodgkin, primary mediastinal and diffuse large B cell lymphomasThe Journal of Pathology, 2005