Inhibition of MMP-dependent chemotaxis and amelioration of experimental autoimmune uveitis with a selective metalloproteinase-2 and -9 inhibitor.
The chemotaxis of inflammatory cells depends on proteolytic disruption of extracellular matrix components. The metalloproteinases (MMP)-2 and -9 enable T-lymphocytes to pass through basement membranes. Selective inhibition of only MMP-2 and -9 almost completely abolished the ability of lymphocytes to digest collagen. The chemotaxis of lymphocytes was reduced 40%. In our in-vivo model of experimental autoimmune uveitis (EAU), 46% of the animals in the treated group remained disease-free, whereas all animals in the control group developed EAU. The mean activity of the disease was also statistically significantly reduced. The data suggest that selective MMP-2 and -9 inhibition might be a treatment option.
El-Shabrawi
Yosuf
Y
Department of Internal Medicine, Medical University, Graz, Austria. yosuf.elshabrawi@meduni-graz.at
Walch
Astrid
A
Hermann
Josef
J
Egger
Gerhard
G
Foster
C Stephen
CS
D020816:Amino Acid Motifs / Q000276:immunology; D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D001485:Basement Membrane / Q000187:drug effects / Q000201:enzymology; D015415:Biomarkers; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000276:immunology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005109:Extracellular Matrix / Q000187:drug effects / Q000201:enzymology; D005260:Female; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use; D012160:Retina / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome; D014605:Uveitis / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology
D015415:Biomarkers; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D010446:Peptide Fragments; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9