title: Delayed Administration of WP1066, an STAT3 Inhibitor, Ameliorates Radiation-Induced Lung Injury in Mice.
abstract: OBJECTIVE
  The present study was designed to investigate the effects of WP1066, a specific inhibitor of STAT3 signaling, on radiation-induced lung injury in mice.
  
  
  METHODS
  C57BL/6J mice were subjected to a single thoracic irradiation of 15 Gy X-ray and WP1066 was administrated through intraperitoneal injection. The early and delayed treatment groups were treated with WP1066 during the first 2 weeks and the second 2 weeks, respectively. The therapeutic effects of WP1066 were evaluated by survival analysis, histological examination, and measurement of inflammatory parameters and collagen deposition. The activation of STAT3 pathway was also estimated by immunohistochemical staining and Western blotting.
  
  
  RESULTS
  Delayed treatment of WP1066, but not early treatment, prolonged survival time and prevented the development of radiation pneumonitis and the subsequent lung fibrosis in mice. WP1066 treatment also significantly suppressed the activation of STAT3 signaling in the irradiated lung tissues.
  
  
  CONCLUSIONS
  The activation of STAT3 pathway might play an important part in the pathogenesis of radiation-induced lung injury. The protective effects of delayed treatment of WP1066 suggested STAT3 signaling could be a therapeutic target for radiation pneumonitis.
authors.affiliation: Department of Radiobiology, School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, 215123, People's Republic of China. yujiahua@suda.edu.cn.
authors.forename: Jiahua
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Radiobiology, School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, 215123, People's Republic of China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Radiobiology, School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, 215123, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Radiobiology, School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, 215123, People's Republic of China.
authors.forename: Kaishuo
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Radiobiology, School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, 215123, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Radiobiology, School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, 215123, People's Republic of China.
authors.forename: Haowen
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Radiobiology, School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, 215123, People's Republic of China. fangsh@suda.edu.cn.
authors.forename: Fenju
authors.initials: F
authors.lastname: Liu
mesh_terms: D000818:Animals; D004334:Drug Administration Schedule; D005260:Female; D005355:Fibrosis; D015870:Gene Expression / Q000187:drug effects; D053583:Interleukin-1beta / Q000097:blood / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D008168:Lung / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011725:Pyridines / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000097:blood*; D011833:Radiation Injuries, Experimental / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D017564:Radiation Pneumonitis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000097:blood / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics; D020032:Tyrphostins / Q000008:administration & dosage*
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D011725:Pyridines; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D020032:Tyrphostins; C519885:WP1066
keywords: Cytokine; Inflammation; Radiation pneumonitis; STAT3; WP1066