title: Regnase-1 in microglia negatively regulates high mobility group box 1-mediated inflammation and neuronal injury.
abstract: Extracellular high mobility group box 1 (HMGB1) has been demonstrated to function as a proinflammatory cytokine and induces neuronal injury in response to various pathological stimuli in central nervous system (CNS). However, the regulatory factor involved in HMGB1-mediated inflammatory signaling is largely unclear. Regulatory RNase 1 (Regnase-1) is a potent anti-inflammation enzyme that can degrade a set of mRNAs encoding proinflammatory cytokines. The present study aims to determine the role of Regnase-1 in the regulation of HMGB1-mediated inflammatory injury in CNS. Cultured microglia and rat brain were treated with recombinant HMGB1 to examine the induction of Regnase-1 expression. Moreover, the role of Regnase-1 in modulating the expression of inflammatory cytokines and neuronal injury was then investigated in microglia by specific siRNA knockdown upon HMGB1 treatment. Results showed that HMGB1 could significantly induce the de novo synthesis of Regnase-1 in cultured microglia. Consistently, Regnase-1 was elevated and found to be co-localized with microglia marker in the brain of rat treated with HMGB1. Silencing Regnase-1 in microglia enhanced HMGB1-induced expression of proinflammatory cytokines and exacerbated neuronal toxicity. Collectively, these results suggest that Regnase-1 can be induced by HMGB1 in microglia and negatively regulates HMGB1-mediated neuroinflammation and neuronal toxicity.
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University. Guangzhou, Guangdong 510515, P. R. China.
authors.forename: Xiao-Xi
authors.initials: XX
authors.lastname: Liu
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University. Guangzhou, Guangdong 510515, P. R. China.|Department of Neurology, the Second Affiliated Hospital &Yuying Children's Hospital, Wenzhou Medical University. Wenzhou, Zhejiang 325000, P. R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University. Guangzhou, Guangdong 510515, P. R. China.
authors.forename: Shao-Fei
authors.initials: SF
authors.lastname: Huang
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University. Guangzhou, Guangdong 510515, P. R. China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University. Guangzhou, Guangdong 510515, P. R. China.
authors.forename: Ya-Fang
authors.initials: YF
authors.lastname: Hu
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University. Guangzhou, Guangdong 510515, P. R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University. Guangzhou, Guangdong 510515, P. R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gu
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D024243:HMGB1 Protein / Q000378:metabolism*; D007249:Inflammation; D008297:Male; D051379:Mice; D017628:Microglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D016207:Cytokines; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; C582808:HMGB1 protein, mouse; C104200:Hbp1 protein, rat; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D014157:Transcription Factors; D012260:Ribonucleases; C510646:ZC3H12A protein, human; C541320:Zc3h12a protein, mouse; C000616614:Zc3h12a protein, rat