In vitro inhibition of matrix metalloproteinase activity in tracheal epithelial lining fluid from horses with recurrent airway obstruction.
OBJECTIVE
To evaluate inhibitory effects of synthetic matrix metalloproteinase (MMP) inhibitors in vitro on gelatinolytic and collagenolytic activities in tracheal epithelial lining fluid (TELF) of horses with recurrent airway obstruction (RAO).


METHODS
10 horses with RAO and 5 healthy control horses.


METHODS
Substrate-based functional assays, collagen I and gelatin degradation, were used to measure endogenous collagenolytic and gelatinolytic activities in TELF. In vitro inhibition of MMP activity in TELF with 2 chemically modified tetracyclines (CMTs; CMT-3 and CMT-8) and 2 bisphosphonates (BPs; zoledronate and pamidronate) was evaluated.


RESULTS
CMT-3, CMT-8, zoledronate, and pamidronate in a dose-dependent manner inhibited TELF type I collagenolytic and gelatinolytic activities, although no complete inhibition of TELF type I collagenolytic and gelatinolytic activities was achieved with the inhibitor concentrations of 25 to 500 microM tested. The CMTs inhibited pathologically induced collagen I degradation more effectively than BPs. Of the tested CMTs, CMT-3 was the most effective inhibitor of gelatinolytic activity, and the efficiency of CMT-3 corresponded with that of the BPs.


CONCLUSIONS
An increase in MMP activity in the equine respiratory tract may potentially be inhibited by administration of CMTs or BPs. Distinct synthetic MMP inhibitors may eventually provide an additional means for pharmacologic treatment by decreasing ongoing active tissue destructive inflammation associated with chronic lung disease. The MMP inhibitors such as CMTs and BPs that are targeted to solely inhibit a pathologic increase in MMP activities provide the advantage of minimal adverse effects that are characteristics of other excessively potent MMP inhibitors.
Raulo
Saara M
SM
Department of Clinical Veterinary Sciences, Faculty of Veterinary Medicine, Helsinki University, Finland.
Sorsa
Timo
T
Maisi
Päivi
P
D000402:Airway Obstruction / Q000201:enzymology*; D000818:Animals; D024042:Collagen Type I / Q000378:metabolism; D004164:Diphosphonates / Q000494:pharmacology; D005780:Gelatin / Q000378:metabolism; D006734:Horse Diseases / Q000201:enzymology*; D006736:Horses; D007093:Imidazoles / Q000494:pharmacology; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism; D000077268:Pamidronate; D020545:Respiratory Mucosa / Q000378:metabolism*; D013754:Tetracyclines / Q000494:pharmacology; D014132:Trachea / Q000378:metabolism*; D000077211:Zoledronic Acid
D024042:Collagen Type I; D004164:Diphosphonates; D007093:Imidazoles; D061965:Matrix Metalloproteinase Inhibitors; D013754:Tetracyclines; C117155:tetracycline CMT-3; C117153:tetracycline CMT-8; D000077211:Zoledronic Acid; D005780:Gelatin; D020782:Matrix Metalloproteinases; D000077268:Pamidronate