Resolvin D1, an endogenous lipid mediator for inactivation of inflammation-related signaling pathways in microglial cells, prevents lipopolysaccharide-induced inflammatory responses.

BACKGROUNDS AND AIM

Microglial cells as an important part of central nervous system (CNS) have generally believed to play significant role in the process leading to a number of neurodegenerative disorders including Parkinson's disease, Alzheimer's disease, prion diseases, multiple sclerosis, HIV-dementia, and stroke. Although different diseases have quite different pathogenesis, the activation of microglia was shared with all of them. Recently, the resolvin D1 (RvD1) as an endogenous antiinflammatory lipid mediator has been confirmed to be involved in the treatment of inflammation-related neuronal injury in neurodegenerative diseases. Therefore, the inhibition of microglia-activated inflammation has been considered as a major treatment strategy in neurodegenerative disease therapy. However, the molecular mechanisms of RvD1 in microglial cells remain unknown and still do not be reported.

METHODS

We taken murine microglia as the experimental sample, and Western blotting, ELISA, reverse-transcriptase PCR, real-time PCR, and electrophoretic mobility shift assay were used to study whether the RvD1 inhibit inflammation of microglial cells. The tumor necrosis factor α (TNF-α), IL-1β, inducible nitric oxide synthase (iNOS) expression, nuclear factor-κB (NF-κB) activation, and mitogen-activated protein kinase (MAPK) pathways were investigated in lipopolysaccharide (LPS)-activated primary microglia.

RESULTS

Our data suggested that RvD1 inhibited the production of LPS-induced microglia inflammatory mediators and TNF-α, IL-1β, and iNOS expression. In addition, according to the study of related signaling pathways, RvD1 attenuated LPS-induced microglia NF-κB activation,MAPK phosphorylation, and activator protein-1 transcriptional activity.

CONCLUSION

This is the first study to demonstrate that RvD1 effects on the reduction of pro-inflammatory responses in LPS-induced microglial cells. The mechanisms underlying these effects may include its potent intracellular NF-κB down-regulation and subsequent pro-inflammatory cytokines release in LPS-activated microglia.