Down-regulation of adhesion molecules and matrix metalloproteinases by ZK 156979 in inflammatory bowel diseases.

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.

• Authors: Maria Martinesi, Cristina Treves, Andrea G Bonanomi, Monica Milla, Siro Bagnoli, Ulrich Zuegel, Andreas Steinmeyer, Maria Stio
• Journal: Clinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 136 Issue 1 Pg. 51-60 (Jul 2010) ISSN: 1521-7035 [Electronic] United States
• PMID: 20399147 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2010 Elsevier Inc. All rights reserved.

Chemical References

• 22-ene-25-oxavitamin D
• Cell Adhesion Molecules
• Immunosuppressive Agents
• Lipopolysaccharides
• Lymphocyte Function-Associated Antigen-1
• Phytohemagglutinins
• Receptors, Calcitriol
• Tumor Necrosis Factor-alpha
• Intercellular Adhesion Molecule-1
• Vitamin D
• Matrix Metalloproteinases
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9

Topics

• Adult
• Aged
• Cell Adhesion Molecules (metabolism)
• Colitis, Ulcerative (metabolism)
• Crohn Disease (metabolism)
• Female
• Humans
• Immunosuppressive Agents (pharmacology)
• Inflammatory Bowel Diseases (metabolism)
• Intercellular Adhesion Molecule-1 (metabolism)
• Leukocytes, Mononuclear (drug effects, metabolism)
• Lipopolysaccharides (pharmacology)
• Lymphocyte Function-Associated Antigen-1 (metabolism)
• Male
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Matrix Metalloproteinases (metabolism)
• Middle Aged
• Phytohemagglutinins (pharmacology)
• Receptors, Calcitriol (metabolism)
• Tumor Necrosis Factor-alpha (metabolism, pharmacology)
• Vitamin D (analogs & derivatives, pharmacology)