title: Transforming growth factor β3 attenuates the development of radiation-induced pulmonary fibrosis in mice by decreasing fibrocyte recruitment and regulating IFN-γ/IL-4 balance.
abstract: Radiation-induced pulmonary fibrosis is a frequently occurred complication from radiotherapy of thoracic tumors. The transforming growth factor-β (TGF-β) superfamily plays a key regulatory role in pulmonary fibrosis. As TGF-β3 showed the potential anti-fibrotic properties especially in scar-less wound healing as opposed to the fibrotic function of TGF-β1, we sought to explore the role of TGF-β3 in radiation-induced pulmonary fibrosis. A single thoracic irradiation of 20 Gy was applied in mice to establish the model of radiation-induced pulmonary fibrosis and the mice were treated by intraperitoneal injections of recombinant TGF-β3 weekly after irradiation. We found that TGF-β3 decelerated the progress of radiation-induced pulmonary fibrosis and hindered the recruitment of fibrocytes to lung. In addition, Th1 response was suppressed as shown by diminished IFN-γ in bronchoalveolar lavage fluid (BALF) after irradiation, and enhancement of Th2 response was marked by increased IL-4 in BALF. TGF-β3 administration significantly attenuated these effects and increased the percentage of Tregs in lung during the progression of pulmonary fibrosis. Taken together, these data suggest that TGF-β3 might be involved in the regulatory mechanism for attenuation of radiation-induced pulmonary fibrosis.
authors.affiliation: Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.
authors.forename: Long
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Xiong
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-0602, USA.
authors.forename: Renfeng
authors.initials: R
authors.lastname: Guo
authors.affiliation: Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.
authors.forename: Qianjun
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.
authors.forename: Fengjun
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Department of Blood Transfusion, Chinese PLA General Hospital, Beijing 100853, PR China.
authors.forename: Haibao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China. Electronic address: aaronpancn@126.com.
authors.forename: Xiujie
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China. Electronic address: zhumx@nic.bmi.ac.cn.
authors.forename: Maoxiang
authors.initials: M
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D003094:Collagen / Q000378:metabolism; D003239:Connective Tissue Cells / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism*; D051379:Mice; D011658:Pulmonary Fibrosis / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D011833:Radiation Injuries, Experimental; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D053782:Transforming Growth Factor beta3 / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D053782:Transforming Growth Factor beta3; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D003094:Collagen
keywords: Cytokine; Fibrocyte; Radiation-induced pulmonary fibrosis; Regulatory T cells; Transforming growth factor-β