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CpG-oligodeoxynucleotides may be effective for preventing ionizing radiation induced pulmonary fibrosis.

Abstract：

: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-γ and IL-12) expression increased. Alveolar macrophage accumulation was reduced in irradiated tissue. Profibrotic cytokine TGF-β1 expression stayed at lower level. In TGF-β1-Smad-dependent pathways, TGF-β1, TβR 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-β1 through stimulating the combination of Th1-promoting and Th2-limiting responses after radiation, and finally inhibited the fibrosis-related downstream TGF-β1-Smad-dependent pathway.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Zhang C,Zhao H,Li BL,Fu-Gao,Liu H,Cai JM,Zheng M

doi

10.1016/j.toxlet.2018.04.009

subject

Has Abstract

pub_date

2018-08-01 00:00:00

pages

181-189

eissn

0378-4274

issn

1879-3169

pii

S0378-4274(18)30138-3

journal_volume

292

pub_type

杂志文章

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