Department of Biochemical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy.
Clin Immunol. 2010 Jul;136(1):51-60. doi: 10.1016/j.clim.2010.03.004. Epub 2010 Apr 15.
Intracellular adhesion molecules and matrix metalloproteinases (MMPs) are up-regulated in intestinal mucosa of patients with inflammatory bowel diseases (IBD), i.e. ulcerative colitis (UC) or Crohn's disease (CD). Our aim was to verify whether the vitamin D analogue ZK 156979 (ZK) down-regulates adhesion molecules, and decreases MMPs production by PBMC of IBD patients. ICAM-1 and LFA-1 levels increase, when PBMC were incubated with PHA or LPS or TNF-alpha, and decrease when these substances were used in combination with ZK. MMPs activity increases incubating the cells with PHA or LPS or TNF-alpha. MMP-9 decreases when ZK was used in association, while MMP-2 decreases only when ZK was used in combination with anti-TNF-alpha. Our results suggest that the down-regulation of ICAM-1 and LFA-1 on PBMC and the inhibition of MMP-9 activity by ZK could provide a potential role of this low calcemic vitamin D derivative in future strategies in IBD therapy.
细胞内黏附分子和基质金属蛋白酶（MMPs）在炎症性肠病（IBD）患者的肠道黏膜中上调，即溃疡性结肠炎（UC）或克罗恩病（CD）。我们的目的是验证维生素 D 类似物 ZK 156979（ZK）是否下调黏附分子，并降低 IBD 患者 PBMC 产生的 MMPs。当 PBMC 与 PHA 或 LPS 或 TNF-α孵育时，ICAM-1 和 LFA-1 水平增加，当这些物质与 ZK 联合使用时，它们的水平降低。当用 PHA 或 LPS 或 TNF-α孵育细胞时，MMPs 活性增加。当与 ZK 联合使用时，MMP-9 减少，而当与抗 TNF-α联合使用时，MMP-2 减少。我们的结果表明，ZK 下调 PBMC 上的 ICAM-1 和 LFA-1 以及抑制 MMP-9 活性可能为这种低钙维生素 D 衍生物在未来 IBD 治疗策略中提供潜在作用。
