The inflammasome accelerates radiation-induced lung inflammation and fibrosis in mice

Sung Hwa Sohn; Ji Min Lee; Soojin Park; Hyun Yoo; Jeong Wook Kang; Dasom Shin; Kyung Hwa Jung; Yun Sil Lee; Jaeho Cho; Hyunsu Bae

doi:10.1016/j.etap.2015.02.019

The inflammasome accelerates radiation-induced lung inflammation and fibrosis in mice

Sung Hwa Sohn, Ji Min Lee, Soojin Park, Hyun Yoo, Jeong Wook Kang, Dasom Shin, Kyung Hwa Jung, Yun Sil Lee, Jaeho Cho, Hyunsu Bae

Department of Radiation Oncology

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

44 Citations (Scopus)

Abstract

Although lung inflammation and fibrosis are well-documented dose-limiting side effects of lung irradiation, the mechanisms underlying these pathologies are unknown. An improved mechanistic understanding of radiation-induced pneumonitis is a prerequisite for the development of more effective radiotherapy; this was the rationale for the current study. Mouse lungs were focally irradiated with 75. Gy. The numbers of neutrophils, lymphocytes, macrophages, and total cells in the bronchoalveolar lavage fluid were counted, and pro-inflammatory cytokine levels were measured. Histological analysis and immunohistochemical staining for Tgf-β1 and Cd68 (a macrophage-specific protein) was also performed. After irradiation, mice developed pneumonitis, and exhibited higher numbers of neutrophils, lymphocytes, eosinophils, macrophages, and total cells compared to controls. In addition, inflammasome (Nlrp3, and caspase 1, Il1a, and Il1β), adhesion molecule (Vcam1), and cytokine (Il6) genes were significantly upregulated in the IR group. Cd68 and Tgfb1 proteins were significantly increased after irradiation. Upregulation of Cd68 and Tgfb1 correlates with the onset of radiation-induced pneumonitis and fibrosis. In addition, radiation-induced pneumonitis and fibrosis are accompanied by upregulation of phenotypic markers of inflammasome activity. Our findings have implications for the onset and exacerbation of damage in normal lung tissue.

Original language	English
Pages (from-to)	917-926
Number of pages	10
Journal	Environmental Toxicology and Pharmacology
Volume	39
Issue number	2
DOIs	https://doi.org/10.1016/j.etap.2015.02.019
Publication status	Published - 2015 Mar 1

Bibliographical note

Funding Information:
This work was supported by the Nuclear Research and Development Program ( NRF-2011-0031695 ) (to JC) and by the Radiation Technology R&D Program ( NRF-2013M2A2A7042978 ) (to JC) through the National Research Foundation of Korea, funded by the Ministry of Science, ICT and Future Planning , as well as by the Kyung Hee University grant (No. 20110690 ) (to HB). The authors would like to thank Dong-Su Jang, MFA, (Medical Illustrator, Medical Research Support Section, Yonsei University College of Medicine, Seoul, Korea) for his help with the illustrations.

Publisher Copyright:
© 2015 Elsevier B.V.

All Science Journal Classification (ASJC) codes

Toxicology
Pharmacology
Health, Toxicology and Mutagenesis

Access to Document

10.1016/j.etap.2015.02.019

Cite this

@article{910cc641f59743059c3b326dcce5e145,

title = "The inflammasome accelerates radiation-induced lung inflammation and fibrosis in mice",

abstract = "Although lung inflammation and fibrosis are well-documented dose-limiting side effects of lung irradiation, the mechanisms underlying these pathologies are unknown. An improved mechanistic understanding of radiation-induced pneumonitis is a prerequisite for the development of more effective radiotherapy; this was the rationale for the current study. Mouse lungs were focally irradiated with 75. Gy. The numbers of neutrophils, lymphocytes, macrophages, and total cells in the bronchoalveolar lavage fluid were counted, and pro-inflammatory cytokine levels were measured. Histological analysis and immunohistochemical staining for Tgf-β1 and Cd68 (a macrophage-specific protein) was also performed. After irradiation, mice developed pneumonitis, and exhibited higher numbers of neutrophils, lymphocytes, eosinophils, macrophages, and total cells compared to controls. In addition, inflammasome (Nlrp3, and caspase 1, Il1a, and Il1β), adhesion molecule (Vcam1), and cytokine (Il6) genes were significantly upregulated in the IR group. Cd68 and Tgfb1 proteins were significantly increased after irradiation. Upregulation of Cd68 and Tgfb1 correlates with the onset of radiation-induced pneumonitis and fibrosis. In addition, radiation-induced pneumonitis and fibrosis are accompanied by upregulation of phenotypic markers of inflammasome activity. Our findings have implications for the onset and exacerbation of damage in normal lung tissue.",

author = "Sohn, {Sung Hwa} and Lee, {Ji Min} and Soojin Park and Hyun Yoo and Kang, {Jeong Wook} and Dasom Shin and Jung, {Kyung Hwa} and Lee, {Yun Sil} and Jaeho Cho and Hyunsu Bae",

note = "Funding Information: This work was supported by the Nuclear Research and Development Program ( NRF-2011-0031695 ) (to JC) and by the Radiation Technology R&D Program ( NRF-2013M2A2A7042978 ) (to JC) through the National Research Foundation of Korea, funded by the Ministry of Science, ICT and Future Planning , as well as by the Kyung Hee University grant (No. 20110690 ) (to HB). The authors would like to thank Dong-Su Jang, MFA, (Medical Illustrator, Medical Research Support Section, Yonsei University College of Medicine, Seoul, Korea) for his help with the illustrations. Publisher Copyright: {\textcopyright} 2015 Elsevier B.V.",

year = "2015",

month = mar,

day = "1",

doi = "10.1016/j.etap.2015.02.019",

language = "English",

volume = "39",

pages = "917--926",

journal = "Environmental Toxicology and Pharmacology",

issn = "1382-6689",

publisher = "Elsevier",

number = "2",

}

TY - JOUR

T1 - The inflammasome accelerates radiation-induced lung inflammation and fibrosis in mice

AU - Sohn, Sung Hwa

AU - Lee, Ji Min

AU - Park, Soojin

AU - Yoo, Hyun

AU - Kang, Jeong Wook

AU - Shin, Dasom

AU - Jung, Kyung Hwa

AU - Lee, Yun Sil

AU - Cho, Jaeho

AU - Bae, Hyunsu

N1 - Funding Information: This work was supported by the Nuclear Research and Development Program ( NRF-2011-0031695 ) (to JC) and by the Radiation Technology R&D Program ( NRF-2013M2A2A7042978 ) (to JC) through the National Research Foundation of Korea, funded by the Ministry of Science, ICT and Future Planning , as well as by the Kyung Hee University grant (No. 20110690 ) (to HB). The authors would like to thank Dong-Su Jang, MFA, (Medical Illustrator, Medical Research Support Section, Yonsei University College of Medicine, Seoul, Korea) for his help with the illustrations. Publisher Copyright: © 2015 Elsevier B.V.

PY - 2015/3/1

Y1 - 2015/3/1

N2 - Although lung inflammation and fibrosis are well-documented dose-limiting side effects of lung irradiation, the mechanisms underlying these pathologies are unknown. An improved mechanistic understanding of radiation-induced pneumonitis is a prerequisite for the development of more effective radiotherapy; this was the rationale for the current study. Mouse lungs were focally irradiated with 75. Gy. The numbers of neutrophils, lymphocytes, macrophages, and total cells in the bronchoalveolar lavage fluid were counted, and pro-inflammatory cytokine levels were measured. Histological analysis and immunohistochemical staining for Tgf-β1 and Cd68 (a macrophage-specific protein) was also performed. After irradiation, mice developed pneumonitis, and exhibited higher numbers of neutrophils, lymphocytes, eosinophils, macrophages, and total cells compared to controls. In addition, inflammasome (Nlrp3, and caspase 1, Il1a, and Il1β), adhesion molecule (Vcam1), and cytokine (Il6) genes were significantly upregulated in the IR group. Cd68 and Tgfb1 proteins were significantly increased after irradiation. Upregulation of Cd68 and Tgfb1 correlates with the onset of radiation-induced pneumonitis and fibrosis. In addition, radiation-induced pneumonitis and fibrosis are accompanied by upregulation of phenotypic markers of inflammasome activity. Our findings have implications for the onset and exacerbation of damage in normal lung tissue.

AB - Although lung inflammation and fibrosis are well-documented dose-limiting side effects of lung irradiation, the mechanisms underlying these pathologies are unknown. An improved mechanistic understanding of radiation-induced pneumonitis is a prerequisite for the development of more effective radiotherapy; this was the rationale for the current study. Mouse lungs were focally irradiated with 75. Gy. The numbers of neutrophils, lymphocytes, macrophages, and total cells in the bronchoalveolar lavage fluid were counted, and pro-inflammatory cytokine levels were measured. Histological analysis and immunohistochemical staining for Tgf-β1 and Cd68 (a macrophage-specific protein) was also performed. After irradiation, mice developed pneumonitis, and exhibited higher numbers of neutrophils, lymphocytes, eosinophils, macrophages, and total cells compared to controls. In addition, inflammasome (Nlrp3, and caspase 1, Il1a, and Il1β), adhesion molecule (Vcam1), and cytokine (Il6) genes were significantly upregulated in the IR group. Cd68 and Tgfb1 proteins were significantly increased after irradiation. Upregulation of Cd68 and Tgfb1 correlates with the onset of radiation-induced pneumonitis and fibrosis. In addition, radiation-induced pneumonitis and fibrosis are accompanied by upregulation of phenotypic markers of inflammasome activity. Our findings have implications for the onset and exacerbation of damage in normal lung tissue.

UR - http://www.scopus.com/inward/record.url?scp=84925355101&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84925355101&partnerID=8YFLogxK

U2 - 10.1016/j.etap.2015.02.019

DO - 10.1016/j.etap.2015.02.019

M3 - Article

C2 - 25805627

AN - SCOPUS:84925355101

SN - 1382-6689

VL - 39

SP - 917

EP - 926

JO - Environmental Toxicology and Pharmacology

JF - Environmental Toxicology and Pharmacology

IS - 2

ER -

The inflammasome accelerates radiation-induced lung inflammation and fibrosis in mice

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this