Thermolysin activates equine lamellar hoof matrix metalloproteinases.
Cultured equine lamellar hoof explants secrete the pro-enzymes matrix metalloproteinase-2 (MMP-2, 72 kDa) and MMP-2 (92 kDa). Untreated explants remained intact when tested on a calibrated force transducer, but when treated with an MMP activator, developed "in-vitro laminitis", separating at the dermal-epidermal junction. Explants treated with the bacterial protease thermolysin separated dose-dependently; this was accompanied by activation of both MMP-2 and -9. Thermolysin-mediated MP activation did not occur in a cell-free system and was not inhibited by the addition of the MMP inhibitor and batimastat. These findings suggest that thermolysin-mediated gelatinase activation is not dependent on membrane-bound matrix metalloproteinase (MT-MMP) activation, providing further evidence that bacteria can produce potent MMP activators that probably facilitate host invasion.
Mungall
B A
BA
Department of Companion Animal Sciences, School of Veterinary Science, St Lucia, Queensland, Australia 4072.
Pollitt
C C
CC
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel / Q000662:veterinary; D006724:Hoof and Claw / Q000187:drug effects* / Q000201:enzymology; D006736:Horses; D066298:In Vitro Techniques; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D061965:Matrix Metalloproteinase Inhibitors; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D013820:Thermolysin / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology
D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D013876:Thiophenes; D010649:Phenylalanine; C080985:batimastat; D020778:Matrix Metalloproteinase 2; D013820:Thermolysin; D020780:Matrix Metalloproteinase 9