1. Down-regulation of adhesion molecules and matrix metalloproteinases by ZK 156979 in inflammatory bowel diseases.
- Author
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Martinesi M, Treves C, Bonanomi AG, Milla M, Bagnoli S, Zuegel U, Steinmeyer A, and Stio M
- Subjects
- Adult, Aged, Colitis, Ulcerative metabolism, Crohn Disease metabolism, Female, Humans, Immunosuppressive Agents pharmacology, Intercellular Adhesion Molecule-1 metabolism, Leukocytes, Mononuclear drug effects, Lipopolysaccharides pharmacology, Lymphocyte Function-Associated Antigen-1 metabolism, Male, Matrix Metalloproteinase 2 metabolism, Matrix Metalloproteinase 9 metabolism, Middle Aged, Phytohemagglutinins pharmacology, Receptors, Calcitriol metabolism, Tumor Necrosis Factor-alpha metabolism, Tumor Necrosis Factor-alpha pharmacology, Vitamin D pharmacology, Cell Adhesion Molecules metabolism, Inflammatory Bowel Diseases metabolism, Leukocytes, Mononuclear metabolism, Matrix Metalloproteinases metabolism, Vitamin D analogs & derivatives
- Abstract
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., ((c) 2010 Elsevier Inc. All rights reserved.)
- Published
- 2010
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