Down-regulation of adhesion molecules and matrix metalloproteinases by ZK 156979 in inflammatory bowel diseases.
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.
Martinesi
Maria
M
Department of Biochemical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy.
Treves
Cristina
C
Bonanomi
Andrea G
AG
Milla
Monica
M
Bagnoli
Siro
S
Zuegel
Ulrich
U
Steinmeyer
Andreas
A
Stio
Maria
M
D000328:Adult; D000368:Aged; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003093:Colitis, Ulcerative / Q000378:metabolism; D003424:Crohn Disease / Q000378:metabolism; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D015212:Inflammatory Bowel Diseases / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D018167:Receptors, Calcitriol / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
C503158:22-ene-25-oxavitamin D; D015815:Cell Adhesion Molecules; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D016169:Lymphocyte Function-Associated Antigen-1; D010835:Phytohemagglutinins; D018167:Receptors, Calcitriol; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D014807:Vitamin D; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9