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

Eun Jung Lee; Jun Won Kim; Hyun Yoo; Woori Kwak; Won Hoon Choi; Seoae Cho; Yu Jeong Choi; Yoon Jin Lee; Jaeho Cho

doi:10.1016/j.bbrc.2015.05.081

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

Eun Jung Lee, Jun Won Kim, Hyun Yoo, Woori Kwak, Won Hoon Choi, Seoae Cho, Yu Jeong Choi, Yoon Jin Lee, Jaeho Cho

Department of Radiation Oncology

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

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-cm² 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.

Original language	English
Pages (from-to)	20-26
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	464
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2015.05.081
Publication status	Published - 2015 Jul 20

Bibliographical note

Funding Information:
This work was supported by the Nuclear Research and Development Program ( NRF-2011-0031695 ) and the Radiation Technology Research and Development Program ( NRF-2013M2A2A7042978 ) through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning and a faculty research grant from Yonsei University College of Medicine for 2014 ( 6-2014-0031 ). The authors thank Dong-Su Jang (Medical illustrator, Medical Research Support Section, Yonsei University College of Medicine, Seoul, Rep of Korea) for his help with the figure.

Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.

All Science Journal Classification (ASJC) codes

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2015.05.081

Cite this

Lee, E. J., Kim, J. W., Yoo, H., Kwak, W., Choi, W. H., Cho, S., Choi, Y. J., Lee, Y. J., & Cho, J. (2015). Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33 secreted from impaired vessels in the skin compared to fractionated irradiation. Biochemical and Biophysical Research Communications, 464(1), 20-26. https://doi.org/10.1016/j.bbrc.2015.05.081

@article{77024f63dc27450480950cbba5db6149,

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

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-cm2 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.",

author = "Lee, {Eun Jung} and Kim, {Jun Won} and Hyun Yoo and Woori Kwak and Choi, {Won Hoon} and Seoae Cho and Choi, {Yu Jeong} and Lee, {Yoon Jin} and Jaeho Cho",

note = "Funding Information: This work was supported by the Nuclear Research and Development Program ( NRF-2011-0031695 ) and the Radiation Technology Research and Development Program ( NRF-2013M2A2A7042978 ) through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning and a faculty research grant from Yonsei University College of Medicine for 2014 ( 6-2014-0031 ). The authors thank Dong-Su Jang (Medical illustrator, Medical Research Support Section, Yonsei University College of Medicine, Seoul, Rep of Korea) for his help with the figure. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc. All rights reserved.",

year = "2015",

month = jul,

day = "20",

doi = "10.1016/j.bbrc.2015.05.081",

language = "English",

volume = "464",

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journal = "Biochemical and Biophysical Research Communications",

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Lee, EJ, Kim, JW, Yoo, H, Kwak, W, Choi, WH, Cho, S, Choi, YJ, Lee, YJ & Cho, J 2015, 'Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33 secreted from impaired vessels in the skin compared to fractionated irradiation', Biochemical and Biophysical Research Communications, vol. 464, no. 1, pp. 20-26. https://doi.org/10.1016/j.bbrc.2015.05.081

Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33 secreted from impaired vessels in the skin compared to fractionated irradiation. / Lee, Eun Jung; Kim, Jun Won; Yoo, Hyun et al.

In: Biochemical and Biophysical Research Communications, Vol. 464, No. 1, 20.07.2015, p. 20-26.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33 secreted from impaired vessels in the skin compared to fractionated irradiation

AU - Lee, Eun Jung

AU - Kim, Jun Won

AU - Yoo, Hyun

AU - Kwak, Woori

AU - Choi, Won Hoon

AU - Cho, Seoae

AU - Choi, Yu Jeong

AU - Lee, Yoon Jin

AU - Cho, Jaeho

N1 - Funding Information: This work was supported by the Nuclear Research and Development Program ( NRF-2011-0031695 ) and the Radiation Technology Research and Development Program ( NRF-2013M2A2A7042978 ) through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning and a faculty research grant from Yonsei University College of Medicine for 2014 ( 6-2014-0031 ). The authors thank Dong-Su Jang (Medical illustrator, Medical Research Support Section, Yonsei University College of Medicine, Seoul, Rep of Korea) for his help with the figure. Publisher Copyright: © 2015 Elsevier Inc. All rights reserved.

PY - 2015/7/20

Y1 - 2015/7/20

N2 - 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-cm2 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.

AB - 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-cm2 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.

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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

Abstract

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