Reactive astrocytes and perivascular macrophages express NLRP3 inflammasome in active demyelinating lesions of multiple sclerosis and necrotic lesions of neuromyelitis optica and cerebral infarction
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.
We studied the expression of NLRP3 inflammasome components in active demyelinating lesions of MS by immunohistochemistry.
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.
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.