Journal
TOXICOLOGY LETTERS
Volume 292, Issue -, Pages 181-189Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2018.04.009
Keywords
Radiation; Pulmonary fibrosis; CpG-ODN; Macrophage; TGF-beta 1; Smad 2/3
Categories
Funding
- National Natural Science Foundation of China [81501623, 81472911]
- Shanghai Municipal and Technology Commission Medical Guide Project [124119b1900]
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Pulmonary fibrosis is a serious adverse effect of radiotherapy for thoracic tumor, which is believed to be a process that is tightly regulated by the phenotype of the developing Th response after radiation. Here, we will investigate whether CpG-oligodeoxynucleotides (ODN) prevent radiation-induced pulmonary fibrosis by shifting the imbalance of Th1 and Th2 response and summarizes the possible mechanism. In this study, female C57BL/6 mice were chosen to preform pulmonary fibrosis model, the whole-thorax of mice was exposed to a single radiation dose of 15 Gy. When irradiated mice were administrated with CpG-ODN, forming of pulmonary fibrosis was significantly prevented. Th2-related cytokines (IL-4 and IL-13) expression decreased, Th1 related-cytokine (IFN-gamma and IL-12) expression increased. Alveolar macrophage accumulation was reduced in irradiated tissue. Profibrotic cytokine TGF-beta 1 expression stayed at lower level. In TGF-beta 1-Smad-dependent pathways, TGF-beta 1, T beta R and phosphor-Smad 2/3 were down regulated, and Smad 7 was up regulated. These suggested that CpG-ODN prevented pulmonary fibrosis after radiation. The mechanism might be associated with reduction of alveolar macrophages accumulation and profibrogenic cytokines secretion TGF-beta 1 through stimulating the combination of Th1-promoting and Th2-limiting responses after radiation, and finally inhibited the fibrosis-related downstream TGF-beta 1-Smad-dependent pathway.
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