Pentoxifylline affects cell proliferation of as well as collagen synthesis and transforming growth factor (TGF)-β1 expression by human fibroblasts derived from keloid / 中华皮肤科杂志

ABSTRACT

Objective To investigate the effects of pentoxifylline on the cell proliferation of, collagen synthesis and TGF-β1 expression by human fibroblasts derived from keloid. Methods Skin samples were obtained from the lesions of 3 patients with keloid and normal skin of 3 human controls followed by primary culture of fibroblasts. Fibroblasts of 5th to 8th generation were cultured with pentoxifylline of 0.1 to 3 g/L for various durations. Then, MTT assay was performed to detect the cell proliferation of fibroblasts, double antibody sandwich-enzyme linked immunosorbent assay (ELISA) to measure the expression of TGF-β1, and reversetranscription PCR to examine the mRNA expressions of procollagen Ⅰ and Ⅲ in these fibroblasts. Results The pentoxifylline of 0.1 to 2 g/L markedly inhibited the proliferation of fibroblasts derived from keloid lesions and normal skin, in a dose- and time-dependent manner, with the strongest effect observed in fibroblasts treated with pentoxifylline of 2 g/L. A significant reduction was induced in the TGF-β1 mRNA expression in keloidand normal skin-derived fibroblasts by pentoxifylline of 0.5 to 2 g/L (all P < 0.01), and in the mRNA expression of procollagen Ⅰ and Ⅲ by pentoxifylline of 1 and 2 g/L (P < 0.05 or 0.01). Concretely, the relative mRNA expression level of procollagen Ⅰ and Ⅲwas 0.873 ± 0.077, 0.571 ± 0.050 respectively in keloid fibroblasts respectively, and 0.473 ± 0.035, 0.370 ± 0.045 in the control fibroblasts, after treated with pentoxifylline of 1 g/L, 0.750 ± 0.036 and 0.433 ± 0.045 respectively in keloid-derived fibroblasts, 0.390 ± 0.030 and 0.250 ±0.123 respectively in the control fibroblasts, after treated with pentoxifylline of 2 g/L, significantly lower than that in the keloid-derived (1.216 ± 0.061 and 0.953 ± 0.060) and control (0.836 ± 0.080 and 0.776 ± 0.041) fibroblasts without treatment. Conclusion Pentoxifylline shows an evident suppressive effect on the cell proliferation of, as well as the expression of TGF-β1 and procollagen Ⅰ and Ⅲ in fibroblasts derived from keloid lesions and normal skin.