PMID- 20148699 OWN - NLM STAT- MEDLINE DCOM- 20100303 LR - 20211020 IS - 1362-3095 (Electronic) IS - 0955-3002 (Print) IS - 0955-3002 (Linking) VI - 86 IP - 2 DP - 2010 Feb TI - Irradiation induces regionally specific alterations in pro-inflammatory environments in rat brain. PG - 132-44 LID - 10.3109/09553000903419346 [doi] AB - PURPOSE: Pro-inflammatory environments in the brain have been implicated in the onset and progression of neurological disorders. In the present study, we investigate the hypothesis that brain irradiation induces regionally specific alterations in cytokine gene and protein expression. MATERIALS AND METHODS: Four month old F344 x BN rats received either whole brain irradiation with a single dose of 10 Gy gamma-rays or sham-irradiation, and were maintained for 4, 8, and 24 h following irradiation. The mRNA and protein expression levels of pro-inflammatory mediators were analysed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining. To elucidate the molecular mechanisms of irradiation-induced brain inflammation, effects of irradiation on the DNA-binding activity of pro-inflammatory transcription factors were also examined. RESULTS: A significant and marked up-regulation of mRNA and protein expression of pro-inflammatory mediators, including tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and monocyte chemoattractant protein-1 (MCP-1), was observed in hippocampal and cortical regions isolated from irradiated brain. Cytokine expression was regionally specific since TNF-alpha levels were significantly elevated in cortex compared to hippocampus (57% greater) and IL-1beta levels were elevated in hippocampus compared to cortical samples (126% greater). Increases in cytokine levels also were observed after irradiation of mouse BV-2 microglial cells. A series of electrophoretic mobility shift assays (EMSA) demonstrated that irradiation significantly increased activation of activator protein-1 (AP-1), nuclear factor-kappaB (NF-kappaB), and cAMP response element-binding protein (CREB). CONCLUSION: The present study demonstrated that whole brain irradiation induces regionally specific pro-inflammatory environments through activation of AP-1, NF-kappaB, and CREB and overexpression of TNF-alpha, IL-1beta, and MCP-1 in rat brain and may contribute to unique pathways for the radiation-induced impairments in tissue function. FAU - Lee, Won Hee AU - Lee WH AD - School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University (Virginia Tech), Blacksburg, Virginia 24061, USA. ywlee@vt.edu FAU - Sonntag, William E AU - Sonntag WE FAU - Mitschelen, Matthew AU - Mitschelen M FAU - Yan, Han AU - Yan H FAU - Lee, Yong Woo AU - Lee YW LA - eng GR - R01NS056218/NS/NINDS NIH HHS/United States GR - R01 NS056218-01A1/NS/NINDS NIH HHS/United States GR - P01 AG011370/AG/NIA NIH HHS/United States GR - R01 NS056218-06/NS/NINDS NIH HHS/United States GR - R01 NS056218-04/NS/NINDS NIH HHS/United States GR - R01 NS056218/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - England TA - Int J Radiat Biol JT - International journal of radiation biology JID - 8809243 RN - 0 (Ccl2 protein, rat) RN - 0 (Chemokine CCL2) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 0 (Interleukin-1beta) RN - 0 (NF-kappa B) RN - 0 (RNA, Messenger) RN - 0 (Transcription Factor AP-1) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Animals MH - Brain/immunology/*metabolism/*radiation effects MH - Cell Line MH - Chemokine CCL2/genetics/metabolism MH - Cyclic AMP Response Element-Binding Protein/metabolism MH - Cytokines/genetics/metabolism MH - Inflammation Mediators/*metabolism MH - Interleukin-1beta/genetics/metabolism MH - Male MH - Mice MH - NF-kappa B/metabolism MH - RNA, Messenger/genetics/metabolism MH - Rats MH - Rats, Inbred BN MH - Rats, Inbred F344 MH - Transcription Factor AP-1/metabolism MH - Tumor Necrosis Factor-alpha/genetics/metabolism MH - Up-Regulation/radiation effects PMC - PMC2827151 MID - NIHMS170032 COIS- Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. EDAT- 2010/02/13 06:00 MHDA- 2010/03/04 06:00 PMCR- 2011/02/01 CRDT- 2010/02/13 06:00 PHST- 2010/02/13 06:00 [entrez] PHST- 2010/02/13 06:00 [pubmed] PHST- 2010/03/04 06:00 [medline] PHST- 2011/02/01 00:00 [pmc-release] AID - 10.3109/09553000903419346 [doi] PST - ppublish SO - Int J Radiat Biol. 2010 Feb;86(2):132-44. doi: 10.3109/09553000903419346.