NLRP3 Inflammasome Is Expressed and Functional in Mouse Brain Microglia but Not in Astrocytes.

Abstract

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.

• Authors: Audrey Gustin, Mélanie Kirchmeyer, Eric Koncina, Paul Felten, Sophie Losciuto, Tony Heurtaux, Aubry Tardivel, Paul Heuschling, Catherine Dostert
• Journal: PloS one (PLoS One) Vol. 10 Issue 6 Pg. e0130624 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26091541 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Carrier Proteins
• Inflammasomes
• Interleukin-18
• Interleukin-1alpha
• Interleukin-1beta
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• Peptide Fragments
• Receptors, Purinergic P2X7
• alpha-Synuclein
• amyloid beta-protein (25-35)
• Caspase 1

Topics

• Amyloid beta-Peptides (toxicity)
• Animals
• Astrocytes (metabolism)
• Brain (cytology)
• Carrier Proteins (genetics, metabolism)
• Caspase 1 (deficiency, genetics, metabolism)
• Cells, Cultured
• Enzyme-Linked Immunosorbent Assay
• Inflammasomes (metabolism)
• Interleukin-18 (metabolism)
• Interleukin-1alpha (metabolism)
• Interleukin-1beta (analysis, metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Microglia (cytology, drug effects, metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein
• Peptide Fragments (toxicity)
• Receptors, Purinergic P2X7 (metabolism)
• alpha-Synuclein (pharmacology)