Reactive astrocytes and perivascular macrophages express NLRP 3 inflammasome in active demyelinating lesions of multiple sclerosis and necrotic lesions of neuromyelitis optica and cerebral infarction
Abstract
Abstract Objective Inflammasome, activated by pathogen‐derived and host‐derived danger signals, constitutes a multimolecular signaling complex that serves as a platform for caspase‐1 (CASP1) activation and interleukin‐1β (IL‐1B) maturation. Mice deficient for NLRP3 inflammasome components are resistant to experimental autoimmune encephalomyelitis (EAE), suggesting a pro‐inflammatory role of NLRP3 inflammasome. However, at present, a pathological role of NLRP3 inflammasome in multiple sclerosis (MS) brains remains unknown. Methods We studied the expression of NLRP3 inflammasome components in active demyelinating lesions of MS by immunohistochemistry. Results Reactive astrocytes and perivascular macrophages expressed all three components of NLRP3 inflammasome – NLRP3, ASC and CASP1 – along with IL‐1B in active demyelinating lesions of MS, active necrotic lesions of neuromyelitis optica (NMO) and acute necrotic lesions of cerebral infarction. In contrast, the levels of expression of NLRP3, ASC, CASP1, and IL‐1B were greatly reduced in chronic inactive lesions of MS and gliotic lesions of cerebral infarction. Furthermore, the great majority of ramified and amoeboid microglia did not express NLRP3 in active and inactive MS lesions. Conclusions NLRP3 inflammasome could be activated chiefly in reactive astrocytes and infiltrating macrophages under the condition of active destruction of brain tissues that potentially provides a danger signal.
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Inflammasome signaling in the CNS has been reported in microglia, astrocytes, perivascular brain-resident macrophages, oligodendrocytes, endothelial cells, and neurons.
“Inflammasome signaling in the CNS has also been reported in the microglia, the brain’s critical innate immune cells (206), in astrocytes (207), perivascular brain-resident macrophages (208), oligodendrocytes (209), endothelial cells (210), as well as in neurons (211).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [208]
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- Authors
- Kawana, N., Yamamoto, Y., Ishida, T., Saito, Y., Konno, H., Arima, K., & Satoh, J.
- Affiliations
- Meiji Pharmaceutical University (JP)
- Kohnodai Hospital, National Center for Global Health and Medicine (JP)
- National Center of Neurology and Psychiatry (JP)
- Sendai Nishitaga National Hospital (JP)
- Corresponding author
- Satoh, Jun‐ichi
- Venue
- Clinical and Experimental Neuroimmunology
- Publisher
- Wiley
- Published
- 2013-11-11
- Volume
- 4
- Issue
- 3
- Pages
- 296-304
- ISSN
- 1759-1961 (ISSN-L)
- OpenAlex
- W2092994936
- Cited by
- 34
- References
- 38
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 6 · 2022: 2 · 2021: 3 · 2020: 5 · 2019: 3 · 2017: 2 · 2016: 4 · 2015: 2 · 2014: 1 · 2013: 1
- FWCI
- 1.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical and Experimental Neuroimmunology (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (25430054)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- NLRP3 inflammasome, multiple sclerosis, neuromyelitis optica, cerebral infarction, reactive astrocytes, perivascular macrophages, caspase-1, IL-1β, ASC, demyelinating lesions, necrotic lesions, microglia, neuroinflammation, damage-associated molecular patterns
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