title: Radiation-induced non-targeted response in vivo: role of the TGFβ-TGFBR1-COX-2 signalling pathway.
abstract: BACKGROUND
  Previous studies from our group and others have shown that cyclooxygenase-2 (COX-2) has an essential role in radiation-induced non-targeted responses and genomic instability in vivo. However, the signalling pathways involved in such effects remain unclear.
  
  
  METHODS
  A 1 cm(2) area (1 cm × 1 cm) in the lower abdominal region of gpt delta transgenic mice was irradiated with 5 Gy of 300 keV X-rays. Nimesulide, a selective COX-2 inhibitor, was given to mice for five consecutive days before irradiation. Changes in transforming growth factor-beta (TGF-β) and TGF-β receptor type-1 (TGFBR1) mediated signalling pathways, in the out of radiation field lung and liver tissues were examined.
  
  
  RESULTS
  While the plasma level of cytokines remained unchanged, the expression of TGF-β and its receptors was elevated in non-targeted lung tissues after partial body irradiation. In contrast to the predominant expression of TGF-β in stromal and alveolar cells, but not in bronchial epithelial cells, TGF-β receptors, especially TGFBR1 were significantly elevated in non-targeted bronchial epithelial cells, which is consistent with the induction of COX-2. The different expression levels of TGFBR1 between liver and lung resulted in a tissue specific induction of COX-2 in these two non-targeted tissues. Multiple TGF-β induced signalling pathways were activated in the non-targeted lung tissues.
  
  
  CONCLUSIONS
  The TGFβ-TGFBR1-COX-2 Signalling Pathway has a critical role in radiation-induced non-targeted response in vivo.
authors: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA.
authors: Y
authors: Y
authors: Chai
authors: R K K
authors: RK
authors: Lam
authors: G M
authors: GM
authors: Calaf
authors: H
authors: H
authors: Zhou
authors: S
authors: S
authors: Amundson
authors: T K
authors: TK
authors: Hei
mesh_terms: D000818:Animals; D024201:Bystander Effect / Q000528:radiation effects; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D008099:Liver / Q000378:metabolism / Q000528:radiation effects*; D008168:Lung / Q000378:metabolism / Q000528:radiation effects*; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction / Q000528:radiation effects*; D013449:Sulfonamides / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014965:X-Rays
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D018125:Receptors, Transforming Growth Factor beta; D013449:Sulfonamides; D016212:Transforming Growth Factor beta; D051546:Cyclooxygenase 2; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625842:Tgfbr1 protein, mouse; C012655:nimesulide