Open AccessResolvin D 1, an Endogenous Lipid Mediator for Inactivation of Inflammation‐Related Signaling Pathways in Microglial Cells, Prevents Lipopolysaccharide‐Induced Inflammatory Responses
Author(s) -
Xu MinXuan,
Tan BingChang,
Zhou Wei,
Wei Ting,
Lai WeiHong,
Tan JingWang,
Dong JiaHong
Publication year - 2013
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12069
Subject(s) - microglia , inflammation , tumor necrosis factor alpha , neuroinflammation , lipopolysaccharide , signal transduction , nitric oxide synthase , immunology , mediator , microbiology and biotechnology , nitric oxide , biology , medicine , chemistry , cancer research , endocrinology
Summary 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, A lzheimer'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 ( R v D 1) 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 R v D 1 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 R v D 1 inhibit inflammation of microglial cells. The tumor necrosis factor α ( TNF ‐α), IL ‐1β, inducible nitric oxide synthase (i NOS ) expression, nuclear factor‐ κ B ( NF ‐ κ B ) activation, and mitogen‐activated protein kinase ( MAPK ) pathways were investigated in lipopolysaccharide ( LPS )‐activated primary microglia. Results Our data suggested that R v D 1 inhibited the production of LPS‐induced microglia inflammatory mediators and TNF ‐α, IL ‐1β, and i NOS expression. In addition, according to the study of related signaling pathways, R v D 1 attenuated LPS ‐induced microglia NF ‐ κ B activation, MAPK phosphorylation, and activator protein‐1 transcriptional activity. Conclusion This is the first study to demonstrate that R v D 1 effects on the reduction of pro‐inflammatory responses in LPS ‐induced microglial cells. The mechanisms underlying these effects may include its potent intracellular NF ‐ κ B down‐regulation and subsequent pro‐inflammatory cytokines release in LPS ‐activated microglia.