The role of NLRC4 inflammasome on intracerebral hemorrhage-caused inflammation in rats
Abstract Background: The NLRC4 inflammasome, a member of nucleotide-binding and oligomerization domain-like receptor (NLR) family, amplifies the neuroinflammation by facilitating the processing of caspase-1, interleukin (IL)–1β and IL-18. We explored whether NLRC4 knockdown alleviated inflammatory injury following intracerebral hemorrhage (ICH). Furthermore, whether NLRC4 inflammasome activation can be adjusted by the RGS2/LRRK2 pathway was investigated.Methods: 50μl arterial blood was drawn and injected into basal ganglions to simulate the ICH model. NLRC4 small interfering RNAs(siRNA) were utilized to knockdown NLRC4. LRRK2 inhibitor (GNE7915) was injected into the abdominal cavity. Short hairpin (sh) RNA lentiviral and lentivirus containing RGS2 were designed and applied to knockdown and promote RGS2 expression. Neurological functions, brain edema, western blot, enzyme-linked immunosorbent, hematoxylin and eosin staining, nissl staining, immunoprecipitation, immunofluorescence assay and evans blue dye extravasation and autofluorescence assay were evaluated.Results: It was shown that the NLRC4 inflammasome was activated following ICH injury. NLRC4 knockdown extenuated neuronal death, damage of the blood-brain barrier, brain edema and neurological deficiencyat 3 d after ICH. NLRC4 knockdown reduced myeloperoxidase (MPO) cells as well as IL-1β and IL-18 following ICH. GNE7915 reduced LRRK2 kinase, the combination of LRRK2 and NLRC4 and NLRC4 inflammasome activation. RGS2 suppressed the combination of LRRK2 and NLRC4,and NLRC4 inflammasome activation though regulating LRRK2 Kinase Activity. Conclusion: Our study demonstrated that the NLRC4 inflammasome may aggravate the inflammatory injury induced by ICH and RGS2/LRRK2 may relieve inflammatory injury by restraining the NLRC4 inflammasome activation.