Bilirubin Induces A1-Like Reactivity of Astrocyte

作者全名："Li, Siyu; Huang, Hongmei; Zhang, Yan; Li, Ling; Hua, Ziyu"

作者地址："[Li, Siyu; Huang, Hongmei; Zhang, Yan; Li, Ling; Hua, Ziyu] Chongqing Med Univ, Dept Neonatol,China Int Sci & Technol Cooperat Ba, Childrens Hosp,Key Lab Child Dev & Disorders,Chon, Minist Educ,Natl Clin Res Ctr Child Hlth & Disord, Chongqing 400014, Peoples R China"

通信作者："Hua, ZY (通讯作者)，Chongqing Med Univ, Dept Neonatol,China Int Sci & Technol Cooperat Ba, Childrens Hosp,Key Lab Child Dev & Disorders,Chon, Minist Educ,Natl Clin Res Ctr Child Hlth & Disord, Chongqing 400014, Peoples R China."

来源：NEUROCHEMICAL RESEARCH

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000880242800001

JCR分区：Q2

影响因子：4.4

年份：2022

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：Bilirubin; A1 astrocytes; NF-kappa B; Caspase-1; Neuroinflammation

摘要："Astrocytes play an important role in the pathogenesis of bilirubin neurotoxicity, and activated astrocytes might be potential mediators of neuroinflammation processes contributing to neuronal cell death and tissue injury. Recent studies have reported that activated microglia induce two types of reactive astrocytes. A1 astrocytes could cause neuronal death and synaptic damage, as well as impaired phagocytosis. Therefore, the purpose of this study was to investigate whether unconjugated bilirubin (UCB)-induced A1-like astrocytes take on a neuroinflammation type and the underlying regulatory mechanisms. In this study, primary cortical astrocytes were treated with UCB in vitro. We detected the expression of complement component 3 (C3), S100 calcium binding protein A10 (S100A10), nuclear factor kappa B (NF-kappa B), NLR family pyrin domain containing 3 (NLRP3), activated caspase-1, gasdermin D N-terminal (GSDMD-N), PSD95, synaptophysin (SYP), the transcription levels of interleukin (IL)-1 beta and IL-18, and the survival rate of astrocytes after UCB treatment. The results showed that an increase in C3 was accompanied by a decrease in S100A10, and that A1-like astrocytes were functionally expressed after UCB stimulation. Meanwhile, the NF-kappa B and caspase-1 pathways were activated after UCB stimulation. After adding the NF-kappa B-specific inhibitor trans-activator of transcriptional-NEMO-binding domain (TAT-NBD) and caspase-1 specific inhibitor VX-765, the survival rate of astrocytes and neurons increased, whereas the protein expression of C3, NF-kappa B, NLRP3, activated caspase-1, and GSDMD-N decreased, and the mRNA levels of IL-1 beta and IL-18 reduced. Thus, we concluded that UCB stimulates the activation of A1-like astrocytes. Inhibition of NF-kappa B and caspase-1 alleviated A1-like astrocytes and exerted anti-inflammatory protective effects."

基金机构：National Natural Science Foundation of China [81971426]; Project of Basic and Frontier Research Plan of Chongqing [CSTC2018jcyjAX0284]; Postgraduate Research Innovation Project of Chongqing [CYS21227]

基金资助正文："This work was supported by the National Natural Science Foundation of China (Grant 81971426), the Project of Basic and Frontier Research Plan of Chongqing (Grant CSTC2018jcyjAX0284) and the Postgraduate Research Innovation Project of Chongqing (Grant CYS21227)."