Anti-inflammatory effects of budesonide in intestinal epithelial cells

Anti-inflammatory effects of budesonide in intestinal epithelial cells
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DOI:
10.1016/j.phrs.2005.06.003
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发表时间:
2005-11-01
影响因子:
9.3
通讯作者:
Peterson, A
Peterson, A
中科院分区:
医学1区
文献类型:
--
作者:
Fredin, MF;Ulfhammer, E;Peterson, A

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糖皮质激素布地奈德是炎症性肠病的主要治疗方法之一。本研究的目的是研究其对Caco-2细胞与LPS刺激的巨噬细胞或与来自相同的条件培养基(CM)共培养后的影响。趋化因子IL-8和ENA-78的mRNA表达在Caco-2细胞中上调,与CM情况相比,这在共培养中总是更明显,其中ENA-78诱导高于IL-8。在Caco-2细胞的顶侧添加布地奈德,以剂量依赖性方式降低IL-8和ENA-78 mRNA水平。在Caco-2细胞的共培养和CM实验中,观察到跨上皮电阻(TEER)的减少和荧光素磺酸(FS)的顶部-基底侧转运的增加。TEER的降低被布地奈德抵消,而对FS转运没有影响。我们的结论是布地奈德发挥抗炎作用,直接对肠上皮细胞,这可能有助于布地奈德在治疗炎症性肠病的整体行动。(c)2005爱思唯尔有限公司保留所有权利。
The glucocorticosteroid budesonide is one of the mainstay treatments in inflammatory bowel disease. The aim of this study was to investigate its effects on Caco-2 cells upon coculture with LPS stimulated macrophages, or with conditioned medium (CM) from the same. The mRNA expression of the chemokines IL-8 and ENA-78 were upregulated in Caco-2 cells, which was always more pronounced in the coculture, as compared to the CM situation, with the ENA-78 induction being higher than of IL-8. Addition of budesonide to the apical side of Caco-2 cells, decreased both IL-8 and ENA-78 mRNA levels in a dose dependent manner. A reduction in trans epithelial electrical resistance (TEER) and an increase in the apical-basolateral transport of fluoresceinated sulfonic acid (FS) were observed in the Caco-2 cells both in cocultures and CM experiments. The reduction in TEER was counteracted by budesonide, whereas it had no effect on the FS transport. We conclude that budesonide exert an anti-inflammatory effect directly on intestinal epithelial cells, which may contribute to the overall action of budesonide in the treatment of inflammatory bowel diseases. (c) 2005 Elsevier Ltd. All rights reserved.