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  2. 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

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

  • Immunol Lett. 2014 Nov;162(1 Pt A):27-33. doi: 10.1016/j.imlet.2014.06.010.
Long Xu 1 Shanshan Xiong 1 Renfeng Guo 2 Zhihua Yang 1 Qianjun Wang 1 Fengjun Xiao 1 Haibao Wang 3 Xiujie Pan 4 Maoxiang Zhu 5
Affiliations

Affiliations

  • 1 Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.
  • 2 Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-0602, USA.
  • 3 Department of Blood Transfusion, Chinese PLA General Hospital, Beijing 100853, PR China.
  • 4 Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China. Electronic address: [email protected].
  • 5 Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China. Electronic address: [email protected].
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.

Keywords

Cytokine; Fibrocyte; Radiation-induced pulmonary fibrosis; Regulatory T cells; Transforming growth factor-β.

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