期刊
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
卷 366, 期 2, 页码 341-348出版社
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/jpet.118.248807
关键词
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资金
- National Natural Sciences Foundation of China [81503106, 81773288, 81372407]
- National Major Scientific and Technological Special Project for Significant New Drugs Development [2018ZX09201001-001-004]
Radiation-induced lung injury (RILI) is the main complication of radiotherapy for thoracic malignancies. Since naringenin, a potent immune-modulator, has been found to relieve bleomycin-induced lung fibrosis by restoring the balance of disordered cytokines, we sought to determine whether naringenin would mitigate RILI and to investigate the underlying mechanism. Animals received fractionated irradiation in the thoracic area to induce RILI. Enzyme-linked immunosorbent assay and MILLIPLEX assays were used for serum and bronchoalveolar lavage fluid for cytokine analyses, hematoxylin and eosin staining for pathologic changes, and Masson trichrome staining for determination of lung fibrosis. Interleukin (IL)-1 beta was found significantly elevated after thoracic irradiation and it triggered production of profibrotic tumor growth factor beta both in vivo and in vitro, suggesting the vital role of in IL-1 beta in the development of RILI. Furthermore, we found that naringenin was able to ameliorate RILI through downregulation of IL-1 beta and restoration of the homeostasis of inflammatory factors. Our results demonstrated that naringenin could serve as a potent immune-modulator to ameliorate RILI. More importantly, we suggest that a new complementary strategy of maintaining the homeostasis of inflammatory factors combined with radiation could improve the efficacy of thoracic radiotherapy.
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