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
  • 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].
PMID: 24996042 DOI: 10.1016/j.imlet.2014.06.010
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.
Products