A Role for the NLR Family Members NLRC4 And NLRP3 in Astrocytic Inflammasome Activation and Astrogliosis Public Deposited

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  • March 20, 2019
Creator
  • Freeman, Leslie
    • Affiliation: School of Medicine, Curriculum in Genetics and Molecular Biology
Abstract
  • The inflammasome is implicated in many inflammatory diseases but has been primarily studied in the macrophage-myeloid lineage. Here we demonstrate a physiologic role for nucleotide-binding domain, leucine-rich repeat, CARD domain containing 4 (NLRC4) in brain astrocytes. NLRC4 has been primarily studied in the context of gram-negative bacteria, where it is required for the maturation of pro-caspase-1 to active caspase-1. We show the heightened expression of NLRC4 protein in astrocytes in a cuprizone model of neuroinflammation and demyelination as well as human multiple sclerotic brains. Similar to macrophages, NLRC4 in astrocytes is required for inflammasome activation by its known agonist, flagellin. However, NLRC4 in astrocytes also mediate inflammasome activation in response to lysophosphatidylcholine (LPC), an inflammatory molecule associated with neurologic disorders. In addition to NLRC4, astrocytic NLRP3 is required for inflammasome activation by LPC. Two biochemical assays show the interaction of NLRC4 with NLRP3, suggesting the possibility of a NLRC4-NLRP3 co-inflammasome.
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Rights statement
  • In Copyright
Advisor
  • Matsushima, Glenn
  • Markovic-Plese, Silva
  • Koller, Beverly H.
  • Kay Lund, Pauline Kay
  • Ting, Jenny P.-Y.
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2016
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