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.

Attenuation of Amiodarone-Induced Pulmonary Fibrosis by Vitamin E Is Associated with Suppression of Transforming Growth Factor-β1Gene Expression but Not Prevention of Mitochondrial Dysfunction

“…Pulmonary expression of TGF-␤ 1 , a major regulator of extracellular matrix components, including collagens, is upregulated in several rodent models of pulmonary fibrosis, including a rat model of AM-induced pulmonary fibrosis (Yi et al, 1996;Iyer et al, 1999;Chung et al, 2001). In the present study, significant up-regulation of TGF-␤ 1 mRNA expression was observed 7 and 21 days after AM treatment, whereas hydroxyproline content was not elevated until 21 days, supporting a central role for this cytokine in the tissue Fig.…”

Ionizing radiation induces myofibroblast differentiation via lactate dehydrogenase

“…It is well-established that radiation causes induction of TGF-␤ (3,24,40), although the mechanisms of radiationinduced TGF-␤ activation are poorly understood. One suggested mechanism is oxidation dependent activation through redox-related mechanisms (4).…”

“…TGF-␤ has been implicated in the development of radiation-induced fibrosis in several organs including the skin, lung, and liver (24,30,40) and TGF-␤ levels in the lung increase in the weeks following thoracic radiation (9,31,40). However, the mechanism of TGF-␤ activation in radiation-induced fibrosis remains poorly understood.…”

Mechanisms of ozone-induced inhibitory effect of bronchoalveolar lavage fluid on alveolar macrophage-mediated immunosuppressive activity in rats

“…It has been reported that granulocyte-macrophage colony-stimulating factor and transforming growth factor ␤ inhibit AM-mediated suppression of lymphocyte proliferation [20]. These cytokines are increased in BALF during lung inflammation [25,26]. Mucin as a component of mucus is also increased in BALF during lung inflammation [27,28].…”