NDLI: Intrinsic apoptosis and proinflammatory cytokines regulated in human astrocytes infected with enterovirus 71.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Wang, Chunyang Zhou, Renmen Zhang, Zerui Jin, Yu Cardona, Carol J. Xing, Zheng
Description	Author Affiliation: Wang C ( 1â The State Key Laboratory of Pharmaceutical Biotechnology and Medical School, Jiangsu Provincial Key Laboratory of Medicine, Nanjing University, Nanjing, PR China 2â Nanjing Children's Hospital, Nanjing, PR China.); Zhou R ( 1â The State Key Laboratory of Pharmaceutical Biotechnology and Medical School, Jiangsu Provincial Key Laboratory of Medicine, Nanjing University, Nanjing, PR China 2â Nanjing Children's Hospital, Nanjing, PR China.); Zhang Z ( 1â The State Key Laboratory of Pharmaceutical Biotechnology and Medical School, Jiangsu Provincial Key Laboratory of Medicine, Nanjing University, Nanjing, PR China.); Jin Y ( 1â The State Key Laboratory of Pharmaceutical Biotechnology and Medical School, Jiangsu Provincial Key Laboratory of Medicine, Nanjing University, Nanjing, PR China 2â Nanjing Children's Hospital, Nanjing, PR China.); Cardona CJ ( 3â College of Veterinary Medicine, University of Minnesota at Twin Cities, Saint Paul, MN 55108, USA.); Xing Z ( 3â College of Veterinary Medicine, University of Minnesota at Twin Cities, Saint Paul, MN 55108, USA 1â The State Key Laboratory of Pharmaceutical Biotechnology and Medical School, Jiangsu Provincial Key Laboratory of Medicine, Nanjing University, Nanjing, PR China.)
Abstract	Enterovirus 71 (EV71) has emerged as a clinically important neurotropic virus following poliovirus eradication. However, the mechanism of EV71-induced neurological manifestation remains largely unclear. In this study, we showed that human astrocytes were susceptible to EV71 and viral RNA was first detected at 12âh post-infection (p.i.), whilst viral proteins were detected at 36âh p.i. EV71-infected astrocytes underwent apoptosis, in which cytochrome c was released from mitochondria to the cytosol and caspase-9 was activated. Interestingly, caspase-2 and -8 were not cleaved or activated during the infection, whilst a selective inhibitor of caspase-9, Z-LEHD-FMK, blocked the cleavage of caspase-3 and -7, indicating that only the mitochondria-mediated intrinsic apoptotic pathway was activated in EV71-infected astrocytes. EV71 infection also induced proinflammatory cytokines, including IL-6, IL-8, CCL5 and IFN-Î³-inducible protein (IP)-10 in astrocytes, which may play a critical role in EV71-induced neuroinflammation and neurological complications. By using inhibitors of mitogen-activated protein kinases (MAPKs), we demonstrated that the induction of the cytokines was mainly regulated by the MAPK p38 signalling pathway as a significant reduction of the cytokines was observed when treated with p38 inhibitors. This study demonstrated that human astrocytes were susceptible to EV71, and the infection led to intrinsic apoptosis and induction of p38-regulated proinflammatory cytokines. These findings further our understanding of the neuropathogenesis in severe cases of EV71 infection.
File Format	HTM / HTML
ISSN	00221317
Issue Number	10
Volume Number	96
e-ISSN	14652099
Journal	Journal of General Virology
Language	English
Publisher	Microbiology Society
Publisher Date	2015-10-01
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Research Support, Non-u.s. Gov't Caspase 9 Cytokines Discipline Virology Astrocytes Humans Cells, Cultured Cytochromes c Biosynthesis Enterovirus A, Human Journal Article Virology Growth & Development Chemistry Immunology Analysis Map Kinase Signaling System Cytoplasm Apoptosis
Content Type	Text
Resource Type	Article
Subject	Virology

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