title: Radiation-induced lung injury in vivo: expression of transforming growth factor-beta precedes fibrosis.
abstract: Cytokine release from irradiated cells has been postulated to start soon after irradiation preceding detectable clinical and pathological manifestation of lung injury. The expression of transforming growth factor beta (TGF beta), a fibrogenic and radiation-inducible cytokine, was studied from 1-16 weeks after the 15 and 30 Gray (Gy) of thoracic irradiation to rats. Thoracic irradiation caused an increase in TGF beta protein in bronchoalveolar lavage (BAL) fluid peaking at 3-6 weeks as compared to sham-irradiated control rats. Steady state TGF beta mRNA expression as shown by whole lung northern blot assay paralleled the TGF beta protein expression in BAL fluid. The peak of TGF beta protein increase in BAL fluid between 3 and 6 weeks coincided with the initial influx of inflammatory cells in BAL fluid, but preceded histologically discernable pulmonary fibrosis that was not apparent until 8-10 weeks after irradiation. In conclusion. TGF beta and mRNA and protein upregulation preceded the radiation-induced pulmonary fibrosis, suggesting a pathogenetic role in the development of radiation fibrosis.
authors.affiliation: Department of Pathology, University of California at San Diego School of Medicine, USA.
authors.forename: E S
authors.initials: ES
authors.lastname: Yi
authors.forename: A
authors.initials: A
authors.lastname: Bedoya
authors.forename: H
authors.initials: H
authors.lastname: Lee
authors.forename: E
authors.initials: E
authors.lastname: Chin
authors.forename: W
authors.initials: W
authors.lastname: Saunders
authors.forename: S J
authors.initials: SJ
authors.lastname: Kim
authors.forename: D
authors.initials: D
authors.lastname: Danielpour
authors.forename: D G
authors.initials: DG
authors.lastname: Remick
authors.forename: S
authors.initials: S
authors.lastname: Yin
authors.forename: T R
authors.initials: TR
authors.lastname: Ulich
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005786:Gene Expression Regulation / Q000528:radiation effects; D007249:Inflammation; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D008297:Male; D011654:Pulmonary Edema / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D011833:Radiation Injuries, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology
chemical_list: D012333:RNA, Messenger; D016212:Transforming Growth Factor beta