The Change of Transforming Growth Factor beta1 (TGF-beta1) Expression by Melatonin in Irradiated Lung / 대한방사선종양학회지

ABSTRACT

PURPOSE: The changed expressions of TGF-beta1, as a key cytokine in the fibrotic process, due to melatonin with potent antioxidative effects, were investigated in the irradiated lung using fibrosis-sensitive C57BL/6 mice. MATERIALS AND METHODS: Female C57BL/6 mice were divided into control irradiation-only, and melatonin (300 mg/kg i.p. 1 hr before irradiation) pretreatment groups. The thoraces of the mice were irradiated with a single dose of 12 Gy. The mRNA expressions of TGF-beta1 in the lung tissue 2 and 4 weeks after irradiation were quantified using semiquantitive RT-PCR, and the cellular origin and expression levels of TGF-beta1 protein were identified using immunohistochemical staining. RESULTS: The relative mRNA expression levels in the irradiation-only and melatonin pretreatment groups 2 and 4 weeks after irradiation were 1.92- and 1.80-fold (p=0.064) and 2.38- and 1.94-fold (p=0.004) increased, respectively compared to those in the control group. Increased expressions of TGF-beta1 protein were prominently detected in regions of histopathological radiation injury, with alveolar macrophages and septal epithelial cells serving as important sources of TGF-beta1 expression. At 2 and 4 weeks after irradiation, the expression levels of protein were 15.8% vs. 16.9% (p=0.565) and 36.1% vs. 25.7% (p=0.009), respectively. CONCLUSION: The mRNA and protein expressions of TGF-beta1 in the lung tissue following thoracic irradiation with 12 Gy were significantly decreased by melatonin pretreatment at 4 weeks. These results indicate that melatonin may have a possible application as an antifibrotic agent in radiation-induced lung injury.