کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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3214226 | 1203276 | 2008 | 11 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: EM703, the new derivative of erythromycin, inhibits transcription of type I collagen in normal and scleroderma fibroblasts EM703, the new derivative of erythromycin, inhibits transcription of type I collagen in normal and scleroderma fibroblasts](/preview/png/3214226.png)
SummaryBackgroundExcessive accumulation of collagen in the skin and internal organs in systemic sclerosis (SSc) is considered to result from enhanced transcription of collagen in fibroblasts. Macrolides have been reported to show various pharmacological activities. Recently, it was reported that EM703, a new derivative of erythromycin, improved bleomycin-induced pulmonary fibrosis in mice.ObjectiveTherefore, we attempted to examine the effects of EM703 on the type I collagen synthetic activity in normal and SSc dermal fibroblasts.MethodsNormal and SSc dermal fibroblasts were cultured with various concentrations of Erythromycin A or EM703 for 48 h. Amount of type I collagen in the culture medium was measured with ELISA with anti-type I collagen antibody. Type I collagen mRNA levels were measured by northern blots analysis and type I collagen transcription and regulation of the human COL1A1 promoter activity were examined by transient transfection and luciferase assay. Electrophoretic gel mobility shift assay was also performed for measurement of binding activities of DNA binding factors to the COL1A1 promoter.ResultsWe found that EM703 reduced collagen production and the mRNA levels of α1(I) collagen in a dose-dependent manner in the normal fibroblasts. The transcription of COL1A1 was downregulated as detected by the luciferase assay. The downregulation was also detected using DNA containing various short lengths of the COL1A1 promoter region. EM703 did not inhibit COL1A1 transcription when the luciferase assay was performed using DNA containing the COL1A1 promoter with a short substitution mutation of the CCAAT box. Decreased production of type I collagen at the transcriptional level was also found in SSc fibroblasts treated with EM703.ConclusionThese results suggest that EM703 inhibits the transcription of type I collagen in both normal and SSc fibroblasts, and that the transcription is inhibited through the CCAAT box of the COL1A1 promoter.
Journal: Journal of Dermatological Science - Volume 49, Issue 3, March 2008, Pages 195–205