Open AccessNLRC5 alleviated OGD/R-induced PC12-cell injury by inhibiting activation of the TLR4/MyD88/NF-κB pathway
Author(s) -
Zhen Zhang,
Yani Sun,
Xin Chen
Publication year - 2020
Publication title -
journal of international medical research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.421
H-Index - 57
eISSN - 1473-2300
pISSN - 0300-0605
DOI - 10.1177/0300060520940455
Subject(s) - tunel assay , apoptosis , reperfusion injury , medicine , superoxide dismutase , oxidative stress , tlr4 , tumor necrosis factor alpha , terminal deoxynucleotidyl transferase , inflammation , microbiology and biotechnology , immunology , biology , ischemia , endocrinology , biochemistry
Objective To assess the role of NOD-like receptor C5 (NLRC5; a major NLRC family protein that regulates immunity, inflammation and tissue fibrosis), in cerebral ischemia-reperfusion injury, characterized by inflammation and oxidative damage.Methods Blood NLRC5 levels were assessed in neonates with cerebral ischemia and in healthy controls. A stable PC12 cell line was established that overexpressed or knocked down NLRC5. Inflammatory responses, apoptosis rate and oxidative damage in PC12 cells under oxygen-glucose deprivation/reperfusion (OGD/R) conditions were evaluated using enzyme-linked immunosorbent assay (ELISA), terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) and reactive oxygen species (ROS) assay.Results Blood NLRC5 levels were suppressed in neonates with cerebral ischemia. ELISAs showed that NLRC5 suppressed levels of tumour necrosis factor-α, interleukin (IL)-6, IL-1β, ROS and superoxide dismutase in OGD/R-treated PC12 cells. Furthermore, NLRC5 overexpression was associated with reduced apoptosis rate in PC12 cells treated by OGD/R. Overexpression of NLRC5 also inhibited levels of toll-like receptor (TLR)4, myeloid differentiation primary response protein MyD88 (MyD88) and phosphorylated nuclear factor kappa B-transcription factor p65 (NF-κB p-p65) in PC12 cells, and decreased nuclear levels of NF-κB p-p65.Conclusion NLRC5 alleviated inflammatory responses, oxidative damage and apoptosis in PC12 cells under OGD/R conditions by suppressing activation of the TLR4/MyD88/NF-κB pathway.