miR‐155 modulates microglia‐mediated immune response by down‐regulating SOCS‐1 and promoting cytokine and nitric oxide production

Abstract

Summary 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.

Staphylococcal Enterotoxin B-Induced MicroRNA-155 Targets SOCS1 To Promote Acute Inflammatory Lung Injury

“…In particular, SOCS1 is induced by IFN-␥ for autoregulation of the IFN-␥ proinflammatory response by inhibiting the JAK/STAT1 signaling pathway (41). Recent experiments in numerous cell types have revealed that miR-155 targets SOCS1 (42)(43)(44). For example, macrophages infected with an RNA virus demonstrated enhanced type I interferon production due to miR-155 targeting of Socs1 (45).…”

MicroRNA 155 Regulates Japanese Encephalitis Virus-Induced Inflammatory Response by Targeting Src Homology 2-Containing Inositol Phosphatase 1

“…miRNA 155 (miR-155) is one of the most widely studied miRNAs in regulating inflammation (12). Silencing miR-155 ameliorates experimental autoimmune encephalomyelitis (13) and regulates inflammatory changes in astrocytes (14) and microglia (15). miR-155 plays a major role in viral infections caused by Epstein-Barr (16), Borna disease (17), and reticuloendotheliosis (18) viruses.…”

Micro RNA-155 participates in re-activation of encephalitogenic T cells

“…Also, miR-155 expression was up-regulated in active brain lesions in multiple sclerosis where it was associated with impaired expression of CD47 in astrocytes and with consequent dysregulation of macrophage inflammatory activity [7]. Moreover, miR-155 was shown of major importance for inflammatory activity of microglia [8]. Finally, it was demonstrated essential for differentiation of Th1 and Th17 cells [9].…”