Leukoregulin is a potent inducer of hyaluronan synthesis in cultured human orbital fibroblasts.

Leukoregulin is a potent inducer of hyaluronan synthesis in cultured human orbital fibroblasts.
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白细胞调节蛋白是培养的人眼眶成纤维细胞中透明质酸合成的有效诱导剂。

DOI:
10.1152/ajpcell.1995.268.2.c382
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发表时间:
1995
期刊:
The American journal of physiology.
影响因子:
--
通讯作者:
Evans,CH
Evans,CH
中科院分区:
--
文献类型:
--
作者:
Smith,TJ;Wang,HS;Evans,CH

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Leukoregulin是一种50 kDa的糖蛋白淋巴因子,可以调节真皮成纤维细胞的细胞外基质。在这里,我们调查leukoregulin对人眼眶成纤维细胞糖胺聚糖合成的影响。我们证明,leukoregulin增强纳入[3 H]葡糖胺糖胺聚糖。在试验浓度范围内(0.1-2 U/ml),该效应呈剂量依赖性,在1 U/ml时最大,且呈时间依赖性。[3 H]糖胺聚糖蓄积在眼眶成纤维细胞株中增加7.67 +/- 1.23倍(SE,n = 7)。脉冲追踪研究表明,这种增强的积累不是大分子降解速率降低的结果。由leukoregulin诱导的放射性标记物质对链霉菌透明质酸酶消化敏感。地塞米松(10(-8)M)和放线菌酮(10微克/毫升)可以阻断细胞因子对透明质酸合成的刺激。[35 S]硫酸盐掺入糖胺聚糖不受白细胞调节蛋白的影响。在真皮成纤维细胞中,白细胞调节素使透明质酸合成增加3.66 +/- 0.37倍(n = 5株,与眼眶相比P < 0.02)。眼眶成纤维细胞中透明质酸合成的增加显著大于先前观察到的其他细胞因子,使得白细胞调节蛋白成为Graves眼病的候选分子触发物。
Leukoregulin, a 50-kDa glycoprotein lymphokine, can regulate the extracellular matrix in dermal fibroblasts. Here we investigate the effects of leukoregulin on the synthesis of glycosaminoglycans in human orbital fibroblasts. We demonstrate that leukoregulin enhances the incorporation of [3H]glucosamine into glycosaminoglycans. The effect is dose dependent in the concentration range tested (0.1-2 U/ml), is maximal at 1 U/ml, and is time dependent. [3H]glycosaminoglycan accumulation is enhanced 7.67 +/- 1.23-fold (SE, n = 7) in orbital fibroblast strains. Pulse-chase studies indicate that this enhanced accumulation is not a result of a decreased rate of macromolecular degradation. Radiolabeled material induced by leukoregulin is sensitive to Streptomyces hyaluronidase digestion. Dexamethasone (10(-8) M) and cycloheximide (10 micrograms/ml) can block the cytokine's stimulation of hyaluronan synthesis. [35S]sulfate incorporation into glycosaminoglycan is unaffected by leukoregulin. In dermal fibroblasts, leukoregulin increased hyaluronan synthesis 3.66 +/- 0.37-fold (n = 5 strains, P < 0.02 compared with orbit). The increase in hyaluronan synthesis in orbital fibroblasts is substantially greater than that observed previously with other cytokines, making leukoregulin a candidate molecular trigger in Graves' ophthalmopathy.