Article: article from journal or magazin.
NLRP3 Inflammasome Is Expressed and Functional in Mouse Brain Microglia but Not in Astrocytes.
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: epublish
Neuroinflammation is the local reaction of the brain to infection, trauma, toxic molecules or protein aggregates. The brain resident macrophages, microglia, are able to trigger an appropriate response involving secretion of cytokines and chemokines, resulting in the activation of astrocytes and recruitment of peripheral immune cells. IL-1β plays an important role in this response; yet its production and mode of action in the brain are not fully understood and its precise implication in neurodegenerative diseases needs further characterization. Our results indicate that the capacity to form a functional NLRP3 inflammasome and secretion of IL-1β is limited to the microglial compartment in the mouse brain. We were not able to observe IL-1β secretion from astrocytes, nor do they express all NLRP3 inflammasome components. Microglia were able to produce IL-1β in response to different classical inflammasome activators, such as ATP, Nigericin or Alum. Similarly, microglia secreted IL-18 and IL-1α, two other inflammasome-linked pro-inflammatory factors. Cell stimulation with α-synuclein, a neurodegenerative disease-related peptide, did not result in the release of active IL-1β by microglia, despite a weak pro-inflammatory effect. Amyloid-β peptides were able to activate the NLRP3 inflammasome in microglia and IL-1β secretion occurred in a P2X7 receptor-independent manner. Thus microglia-dependent inflammasome activation can play an important role in the brain and especially in neuroinflammatory conditions.
Amyloid beta-Peptides/toxicity, Animals, Astrocytes/metabolism, Brain/cytology, Carrier Proteins/genetics, Carrier Proteins/metabolism, Caspase 1/deficiency, Caspase 1/genetics, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Inflammasomes/metabolism, Interleukin-18/metabolism, Interleukin-1alpha/metabolism, Interleukin-1beta/analysis, Interleukin-1beta/metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Microglia/cytology, Microglia/drug effects, Peptide Fragments/toxicity, Receptors, Purinergic P2X7/metabolism, alpha-Synuclein/pharmacology
Web of science
Last modification date