Martinesi Maria, Ambrosini Stefano, Treves Cristina, Zuegel Ulrich, Steinmeyer Andreas, Vito Annese, Milla Monica, Bonanomi Andrea G, Stio Maria
Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy.
Clinical Sciences, Global Biomarker, Global Discovery, Bayer Healthcare, Bayer, 10178 Berlin, Germany.
J Crohns Colitis. 2014 Sep;8(9):1062-71. doi: 10.1016/j.crohns.2014.02.005. Epub 2014 Mar 12.
The adhesion molecule expression and matrix metalloproteinases (MMPs) are proposed to be major factors for intestinal injury mediated by T cells in (IBD) and are up-regulated in intestinal mucosa of IBD patients. To investigate the effect of vitamin D derivatives on adhesion molecules and MMPs in colonic biopsies of IBD patients.
Biopsies from inflamed and non-inflamed tract of terminal ileum and colon and PBMC from the same IBD patients were cultured with or without vitamin D derivatives. MMP activity and adhesion molecule levels were determined.
1,25(OH)2D3 and ZK 191784 significantly decrease ICAM-1 protein levels in the biopsies obtained only from the inflamed region of intestine of UC patients, while MAdCAM-1 levels decrease in the presence of 1,25(OH)2D3 in the non-inflamed region, and, in the presence of ZK, in the inflamed one. In CD patients 1,25(OH)2D3 and ZK decrease ICAM-1 and MAdCAM-1 in the biopsies obtained from the non-inflamed and inflamed regions, with the exception of ICAM-1 in the inflamed region in the presence of 1,25(OH)2D3. The expression of MMP-9, MMP-2, and MMP-3 decreases in the presence of vitamin D derivatives in UC and CD with the exception of 1,25(OH)2D3 that does not affect the levels of MMP-9 and MMP-2 in CD. Vitamin D derivatives always affect MMP-9, MMP-2 and ICAM-1 in PBMC of UC and CD patients.
Based on the increased expression of ICAM-1, MAdCAM-1 and MMP-2,-9,-3 in IBD, our study suggests that vitamin D derivatives may be effective in the management of these diseases.
黏附分子表达和基质金属蛋白酶（MMPs）被认为是炎症性肠病（IBD）中T细胞介导的肠道损伤的主要因素，且在IBD患者的肠黏膜中上调。本研究旨在探讨维生素D衍生物对IBD患者结肠活检组织中黏附分子和MMPs的影响。
将来自同一IBD患者的回肠末端和结肠炎症及非炎症部位的活检组织以及外周血单个核细胞（PBMC），分别在添加或不添加维生素D衍生物的条件下进行培养。测定MMP活性和黏附分子水平。
1,25(OH)₂D₃和ZK 191784仅在溃疡性结肠炎（UC）患者肠道炎症部位的活检组织中显著降低细胞间黏附分子-1（ICAM-1）蛋白水平；而黏膜血管地址素细胞黏附分子-1（MAdCAM-1）水平在非炎症部位添加1,25(OH)₂D₃时降低，在炎症部位添加ZK时降低。在克罗恩病（CD）患者中，1,25(OH)₂D₃和ZK降低非炎症和炎症部位活检组织中的ICAM-1和MAdCAM-1，但在炎症部位添加1,25(OH)₂D₃时ICAM-1除外。在UC和CD中，除1,25(OH)₂D₃不影响CD中MMP-9和MMP-2水平外，维生素D衍生物存在时MMP-9、MMP-2和MMP-3的表达降低。维生素D衍生物总是影响UC和CD患者PBMC中的MMP-9、MMP-2和ICAM-1。
基于IBD中ICAM-1、MAdCAM-1和MMP-2、-9、-3表达增加，本研究提示维生素D衍生物可能对这些疾病的治疗有效。
