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Shvoong Home>Medicine & Health>Effects of colchicine on synthesis and excretion of cytokines and extracellular matrix by human rena Summary

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Effects of colchicine on synthesis and excretion of cytokines and extracellular matrix by human rena

Article Abstract by: TsingHua    

Original Author: Chinese Journal of Pediatrics
Objective Renal interstitial fibrosis is the final common pathway leading to end stage renal failure for progressive renal
disease of various types. The present study was undertaken to add to the knowledge on colchicine′s antiinflammatory and antifibrotic properties confirmed by both human and experimental studies. As the main effector cells, fibroblasts have a central role in the pathogenesis of renal fibrosis. This study aimed to investigate the effects of colchicine on the synthesis and excretion of cytokines transforming growth factor β1 (TGF β1), interleukin 1β (IL 1β) and extracellular matrix (collagen Ⅲ, collagen Ⅳ) in human renal fibroblast. Methods Various concentrations of colchicine (5 0 μmol/L, 10 0 μmol/L,20 0 μmol/L, 40 0 μmol/L) were used to pretreat human embryo renal fibroblasts for 1 hour which were cultured in vitro and then stimulated by 10 0 μg/ml of lipopolysaccharide (LPS). After 18 hours, these fibroblasts and their supernatant were collected. The expression of TGF β1 mRNA, IL 1β mRNA in the cells was studied by using RT PCR, and the excretion of TGF β1, IL 1β, collagen Ⅲ and collagen IV by the fibroblasts was assessed by ELISA respectively. Results (1) By pure stimulation with 10 0 μg/ml LPS,the expression of TGF β1 mRNA and IL 1β mRNA of fibroblasts was up regulated 3 times (66 1±1 6 vs 22 3±2 0, q =590 5, P =0 002) and 4 7 times (22 0±2 2 vs 4 7±0 8, q =106 8, P =0 009), respectively. The protein excretion of TGF β1 and IL 1β was remarkably increased as well compared with the control group . (2) Colchicine could inhibit the expression of TGF β1 mRNA and protein in a dose dependent manner. IL 1β mRNA and protein were both up regulated by colchicine. (3) LPS could not stimulate the excretion of extracellular matrix by fibroblasts, but the excretion of collagen Ⅲ and collagen Ⅳ was down regulated by colchicine in a dose dependent manner. Conclusion (1) The expression of TGF β1 mRNA and the excretion of TGF β1 protein in the fibroblasts was significantly suppressed by colchicine, while the expression of IL 1β mRNA and the excretion of IL 1β protein were enhanced. (2) Colchicine has significant inhibitory effect on the excretion of extracellular matrix such as collagen Ⅲ and collagen Ⅳ in fibroblasts.
Published: July 30, 2004
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