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Abstract
The purpose of the present study was to compare the effects of different doses of ultraviolet radiation A1 (UVA1) on human fibroblast proliferation and collagen level in a mouse model of scleroderma, so as to identify appropriate irradiation doses for clinical treatment of scleroderma. Monolayer from human fibroblasts was cultured in vitro, and a mouse model of scleroderma was established by subcutaneous injection of 100 μL of 400 μg/mL bleomycin into the back of BALB/c mice for 4 weeks. The mouse models and human fibroblasts were divided into UVA1- exposed (100, 60 and 20 J/cm2) and UVA-unexposed groups. At 0, 24 and 48 h after exposure, cell proliferation and levels of hydroxyproline and collagen were detected. UVA1 irradiation was performed 3 times weekly for 10 weeks, and the pathological changes of skin tissues, skin thickness and collagen level were observed after phototherapy. Cell proliferation and the levels of hydroxyproline and collagen were inhibited after phototherapy, and there was a significant difference between the UVA1-exposed cells and UVA1-unexposed cells (P < 0.001). In addition, UVA1 phototherapy improved dermal sclerosis and softened the skin, and there were significant differences between the high-dose UVA1 group and the model group, and the negative group (P < 0.05). It is concluded that UVA1 radiation can reduce cell proliferation, and decrease hydroxyproline and collagen levels in a dose-dependent manner in vitro. High-dose UVA1 phototherapy has marked therapeutic effect on scleroderma in the mouse model. Decreased collagen level may be related to the reduced number and activity of cells, as well as inhibition of collagen synthesis.
Highlights
Scleroderma is a chronic connective tissue disorder of heterogeneous clinical manifestations often with a progressive course
Others[3,7,8,9] reported that medium-dose (60 J/cm2) and low-dose (20-30 J/cm2) ultraviolet radiation A1 (UVA1) therapy was effective against localized scleroderma, and there was no significant difference in clinical scores between the medium-dose (60 J/cm2) and low-dose (20 J/ cm2)
Fibroblast growth was inhibited following UVA1 irradiation and the inhibition gradually increased in a dose-dependent manner, with the most critical damage at 24 h in the high-dose UVA1 group
Summary
Scleroderma is a chronic connective tissue disorder of heterogeneous clinical manifestations often with a progressive course. UVA1 (wavelength: 340-400 nm) phototherapy is a new physical therapy in recent years, which is effective in the treatment of scleroderma and other connective tissue diseases[2,3]. Stege and colleagues[6] found that high-dose (130 J/cm2) UVA1 irradiation was superior to low-dose (20 J/cm2) UVA1 therapy in the treatment of localized scleroderma, and the effectiveness was dose dependent. Others[3,7,8,9] reported that medium-dose (60 J/cm2) and low-dose (20-30 J/cm2) UVA1 therapy was effective against localized scleroderma, and there was no significant difference in clinical scores between the medium-dose (60 J/cm2) and low-dose (20 J/ cm). The purpose of this study was to investigate the mechanism of UVA1 phototherapy and the appropriate dose of irradiation for clinical treatment of scleroderma in a mouse model[11]
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