25-Hydroxycholesterol amplifies microglial IL-1β production in an apoE isoform-dependent manner
Lipopolysaccharides
0301 basic medicine
Interleukin-1beta
610
Mice, Transgenic
tau Proteins
Transgenic
Mice
03 medical and health sciences
Apolipoproteins E
0302 clinical medicine
Alzheimer Disease
616
Medicine and Health Sciences
Animals
Humans
RC346-429
Psychiatry
Inflammation
Amyloid beta-Peptides
Research
Interleukin-1β
Hydroxycholesterols
Frontal Lobe
3. Good health
Lipid metabolism
Steroid Hydroxylases
Apolipoprotein E
Neurology. Diseases of the nervous system
Microglia
Alzheimer’s disease
DOI:
10.1186/s12974-020-01869-3
Publication Date:
2020-06-17T07:02:48Z
AUTHORS (14)
ABSTRACT
Genome-wide association studies of Alzheimer's disease (AD) have implicated pathways related to lipid homeostasis and innate immunity in AD pathophysiology. However, the exact cellular chemical mediators neuroinflammation remain poorly understood. The oxysterol 25-hydroxycholesterol (25-HC) is an important immunomodulator produced by peripheral macrophages with wide-ranging effects on cell signaling immunity. Cholesterol 25-hydroxylase (CH25H), enzyme responsible for 25-HC production, has also been found be one disease-associated microglial (DAM) genes that are upregulated brain transgenic mouse models. We used real-time PCR immunoblotting examine CH25H expression human tissue tissue-bearing amyloid-β plaques or tau pathology. immune response primary microglia under different treatment conditions bearing genetic backgrounds was analyzed using ELISA, western blotting, immunocytochemistry. Treatment toll-like receptor 4 (TLR4) agonist lipopolysaccharide (LPS) markedly upregulates stimulates secretion microglia. LPS-induced production pro-inflammatory cytokine IL-1β potentiated attenuated deletion CH25H. Microglia expressing apolipoprotein E4 (apoE4), a risk factor AD, produce greater amounts than apoE3-expressing following LPS. Remarkably, results level LPS-activated apoE4-expressing apoE2- Blocking potassium efflux inhibiting caspase-1 prevents 25-HC-potentiated release microglia, indicating involvement inflammasome activity. may function as microglial-secreted inflammatory mediator brain, promoting IL-1β-mediated apoE isoform-dependent manner (E4>>E2/E3) thus AD.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (100)
CITATIONS (82)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....