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Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33 secreted from impaired vessels in the skin compared to fractionated irradiation

Authors
 Eun-Jung Lee  ;  Jun Won Kim  ;  Hyun Yoo  ;  Woori Kwak  ;  Won Hoon Choi  ;  Seoae Cho  ;  Yu Jeong Choi  ;  Yoon-Jin Lee  ;  Jaeho Cho 
Citation
 Biochemical and Biophysical Research Communications, Vol.464(1) : 20-26, 2015 
Journal Title
 Biochemical and Biophysical Research Communications 
ISSN
 0006-291X 
Issue Date
2015
Abstract
We have revealed in a porcine skin injury model that eosinophil recruitment was dose-dependently enhanced by a single high-dose irradiation. In this study, we investigated the underlying mechanism of eosinophil-associated skin fibrosis and the effect of high-dose-per-fraction radiation. The dorsal skin of a mini-pig was divided into two sections containing 4-cm(2) fields that were irradiated with 30 Gy in a single fraction or 5 fractions and biopsied regularly over 14 weeks. Eosinophil-related Th2 cytokines such as interleukin (IL)-4, IL-5, and C-C motif chemokine-11 (CCL11/eotaxin) were evaluated by quantitative real-time PCR. RNA-sequencing using 30 Gy-irradiated mouse skin and functional assays in a co-culture system of THP-1 and irradiated-human umbilical vein endothelial cells (HUVECs) were performed to investigate the mechanism of eosinophil-mediated radiation fibrosis. Single high-dose-per-fraction irradiation caused pronounced eosinophil accumulation, increased profibrotic factors collagen and transforming growth factor-β, enhanced production of eosinophil-related cytokines including IL-4, IL-5, CCL11, IL-13, and IL-33, and reduced vessels compared with 5-fraction irradiation. IL-33 notably increased in pig and mouse skin vessels after single high-dose irradiation of 30 Gy, as well as in irradiated HUVECs following 12 Gy. Blocking IL-33 suppressed the migration ability of THP-1 cells and cytokine secretion in a co-culture system of THP-1 cells and irradiated HUVECs. Hence, high-dose-per-fraction irradiation appears to enhance eosinophil-mediated fibrotic responses, and IL-33 may be a key molecule operating in eosinophil-mediated fibrosis in high-dose-per fraction irradiated skin.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/140847
DOI
10.1016/j.bbrc.2015.05.081
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실)
Yonsei Authors
김준원(Kim, Jun Won) ; 이은정(Lee, Eun Jung) ; 조재호(Cho, Jae Ho) ; 최원훈(Choi, Won Hoon)
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http://www.sciencedirect.com/science/article/pii/S0006291X15300073
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