title: Radiation-induced lung fibrosis in a tumor-bearing mouse model is associated with enhanced Type-2 immunity.
abstract: Lung fibrosis may be associated with Type-2 polarized inflammation. Herein, we aim to investigate whether radiation can initiate a Type-2 immune response and contribute to the progression of pulmonary fibrosis in tumor-bearing animals. We developed a tumor-bearing mouse model with Lewis lung cancer to receive either radiation therapy alone or radiation combined with Th1 immunomodulator unmethylated cytosine-phosphorothioate-guanine containing oligodeoxynucleotide (CpG-ODN). The Type-2 immune phenotype in tumors and the histological grade of lung fibrosis were evaluated in mice sacrificed three weeks after irradiation. Mouse lung tissues were analyzed for hydroxyproline and the expression of Type-1/Type-2 key transcription factors (T-bet/GATA-3). The concentration of Type-1/Type-2 cytokines in serum was measured by cytometric bead array. Lung fibrosis was observed to be more serious in tumor-bearing mice than in normal mice post-irradiation. The fibrosis score in irradiated tumor-bearing mice on Day 21 was 4.33 ± 0.82, which was higher than that of normal mice (2.00 ± 0.63; P < 0.05). Hydroxyproline and GATA-3 expression were increased in the lung tissues of tumor-bearing mice following irradiation. CpG-ODN attenuated fibrosis by markedly decreasing GATA-3 expression. Serum IL-13 and IL-5 were elevated, whereas INF-γ and IL-12 expression were decreased in irradiated tumor-bearing mice. These changes were reversed after CpG-ODN treatment. Thus, Type-2 immunity in tumors appeared to affect the outcome of radiation damage and might be of interest for future studies on developing approaches in which Type-1-related immunotherapy and radiotherapy are used in combination.
authors.affiliation: Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, 169 Dong Hu Road, Wuhan, Hubei 430071, P.R. China Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, 169 Dong Hu Road, Wuhan, Hubei 430071, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, 169 Dong Hu Road, Wuhan, Hubei 430071, P.R. China Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, 169 Dong Hu Road, Wuhan, Hubei 430071, P.R. China.
authors.forename: Yacheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, 169 Dong Hu Road, Wuhan, Hubei 430071, P.R. China Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, 169 Dong Hu Road, Wuhan, Hubei 430071, P.R. China.
authors.forename: Zijie
authors.initials: Z
authors.lastname: Mei
authors.affiliation: Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, 169 Dong Hu Road, Wuhan, Hubei 430071, P.R. China Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, 169 Dong Hu Road, Wuhan, Hubei 430071, P.R. China.
authors.forename: Shimin
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, 169 Dong Hu Road, Wuhan, Hubei 430071, P.R. China Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, 169 Dong Hu Road, Wuhan, Hubei 430071, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, 169 Dong Hu Road, Wuhan, Hubei 430071, P.R. China Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, 169 Dong Hu Road, Wuhan, Hubei 430071, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, 169 Dong Hu Road, Wuhan, Hubei 430071, P.R. China Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, 169 Dong Hu Road, Wuhan, Hubei 430071, P.R. China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, 169 Dong Hu Road, Wuhan, Hubei 430071, P.R. China Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, 169 Dong Hu Road, Wuhan, Hubei 430071, P.R. China chxie_65@hotmail.com.
authors.forename: Conghua
authors.initials: C
authors.lastname: Xie
mesh_terms: D000818:Animals; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D007109:Immunity / Q000187:drug effects; D008175:Lung Neoplasms / Q000532:radiotherapy*; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000494:pharmacology; D010641:Phenotype; D010766:Phosphorylation / Q000187:drug effects; D011658:Pulmonary Fibrosis / Q000097:blood / Q000209:etiology* / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011832:Radiation Injuries / Q000097:blood / Q000150:complications* / Q000276:immunology*; D012074:Remission Induction; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D014965:X-Rays; D000098815:T-bet Transcription Factor
chemical_list: C408982:CPG-oligonucleotide; D016207:Cytokines; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D050791:STAT Transcription Factors; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor
keywords: Type-1/Type-2; fibrosis; immune imbalance; radiation-induced lung injury; tumor-bearing