NLRP3 Inflammasome Is Expressed and Functional in Mouse Brain Microglia but Not in Astrocytes
| Autor: | Paul Heuschling, Sophie Losciuto, Catherine Dostert, Mélanie Kirchmeyer, Audrey Gustin, Eric Koncina, Tony Heurtaux, Aubry Tardivel, Paul Felten |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Chemokine
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 Inflammasomes Interleukin-1beta Caspase 1 lcsh:Medicine Multidisciplinary general & others [F99] [Life sciences] Multidisciplinaire généralités & autres [F99] [Sciences du vivant] chemistry.chemical_compound Immune system Interleukin-1alpha NLR Family Pyrin Domain-Containing 3 Protein medicine Secretion lcsh:Science Neuroinflammation Alpha-synuclein Amyloid beta-Peptides Multidisciplinary biology Microglia lcsh:R Interleukin-18 Brain Inflammasome Peptide Fragments Cell biology medicine.anatomical_structure chemistry Astrocytes Immunology alpha-Synuclein biology.protein lcsh:Q Receptors Purinergic P2X7 Carrier Proteins Research Article medicine.drug |
| Zdroj: | PLoS ONE, Vol 10, Iss 6, p e0130624 (2015) PLoS ONE, 10(6). San Franscisco, CA: Public Library of Science (2015). PLoS ONE Plos One, vol. 10, no. 6, pp. e0130624 |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|