title: PIDD Mediates Radiation-Induced Microglia Activation.
abstract: Radiation-induced brain injury (RIBI) is the most common adverse effect that occurs after cranial radiation therapy (CRT). We have previously reported that CRT-induced release of pro-inflammatory cytokines in brain tissues and inhibition of neurogenesis in the hippocampus might be caused by microglial activation and may play an important role in RIBI. In this study we examined the role of p53-induced protein with a death domain (PIDD) in radiation-induced activation of BV-2 cells. BV-2 cells were transfected with antisense oligonucleotide control mRNA or antisense oligonucleotide-targeted PIDD mRNA and were sham or 16 Gy irradiated. The state of microglia and expression of pro-inflammatory cytokines were detected using real-time polymerase chain reaction, Western blotting, immunofluorescence and flow cytometry. Findings from this study suggest that silencing PIDD expression could inhibit microglial activation by downregulating the PIDD-C/NF-κβ transcription pathway. PIDD acts as a critical switcher between the NF-κβ transcription pathway and radiation-induced apoptosis. Given these findings, this study offers a potential novel approach to further combination treatment of RIBI.
authors.affiliation: a   Lung Cancer and Gastroenterology Department, Hunan Cancer Hospital, Affiliated Tumor Hospital of Xiangya Medical School of Central South University, Changsha, 410006, China; and.
authors.forename: Nong
authors.initials: N
authors.lastname: Yang
authors.affiliation: b   Cancer Center.
authors.forename: Xican
authors.initials: X
authors.lastname: Gao
authors.affiliation: b   Cancer Center.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Qu
authors.affiliation: b   Cancer Center.
authors.forename: Ruiguang
authors.initials: R
authors.lastname: Zhang
authors.affiliation: b   Cancer Center.
authors.forename: Fan
authors.initials: F
authors.lastname: Tong
authors.affiliation: b   Cancer Center.
authors.forename: Qian
authors.initials: Q
authors.lastname: Cai
authors.affiliation: c   Experimental Center and.
authors.forename: Jihua
authors.initials: J
authors.lastname: Dong
authors.affiliation: d   Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hu
authors.affiliation: b   Cancer Center.
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
authors.affiliation: b   Cancer Center.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Dong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D002453:Cell Cycle / Q000528:radiation effects; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D016922:Cellular Senescence / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D004260:DNA Repair / Q000528:radiation effects; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000528:radiation effects; D020868:Gene Silencing; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects*; D016328:NF-kappa B / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011836:Radiation Tolerance / Q000235:genetics; D015398:Signal Transduction / Q000528:radiation effects
chemical_list: D053418:Death Domain Receptor Signaling Adaptor Proteins; D018836:Inflammation Mediators; D016328:NF-kappa B; C414729:Pidd1 protein, mouse; D012333:RNA, Messenger