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.
authors: Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, South Korea.
authors: Sung-Hwa
authors: SH
authors: Sohn
authors: Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, South Korea.
authors: Ji Min
authors: JM
authors: Lee
authors: Department of Physiology, College of Oriental Medicine, Kyung Hee University, Seoul, South Korea.
authors: Soojin
authors: S
authors: Park
authors: Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, South Korea.
authors: Hyun
authors: H
authors: Yoo
authors: Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, South Korea.
authors: Jeong Wook
authors: JW
authors: Kang
authors: Department of Physiology, College of Oriental Medicine, Kyung Hee University, Seoul, South Korea.
authors: Dasom
authors: D
authors: Shin
authors: Department of Physiology, College of Oriental Medicine, Kyung Hee University, Seoul, South Korea.
authors: Kyung-Hwa
authors: KH
authors: Jung
authors: College of Pharmacy & Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, South Korea.
authors: Yun-Sil
authors: YS
authors: Lee
authors: Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, South Korea. Electronic address: jjhmd@yuhs.ac.
authors: Jaeho
authors: J
authors: Cho
authors: Department of Physiology, College of Oriental Medicine, Kyung Hee University, Seoul, South Korea. Electronic address: hbae@khu.ac.kr.
authors: Hyunsu
authors: H
authors: Bae
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics*; D020170:Caspase 1 / Q000235:genetics; D002452:Cell Count; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D005260:Female; D005355:Fibrosis; D058847:Inflammasomes / Q000235:genetics*; D008168:Lung / Q000473:pathology; D008810:Mice, Inbred C57BL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology; D011833:Radiation Injuries, Experimental / Q000276:immunology* / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D002352:Carrier Proteins; D020170:Caspase 1; D016207:Cytokines; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D019010:Vascular Cell Adhesion Molecule-1; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C492716:Nlrp3 protein, mouse
keywords: Fibrosis; Inflammasome; Pneumonitis; Radiotherapy