title: Metalloproteinases and their inhibitors are influenced by inhalative glucocorticoid therapy in combination with environmental dust reduction in equine recurrent airway obstruction.
abstract: BACKGROUND
  Overexpression of matrix-metalloproteinases (MMPs) has been shown to lead to tissue damage in equine recurrent airway obstruction (RAO), as a misbalance with their natural inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), occurs. This favors irreversible pulmonary fibrosis formation. Increased levels of MMPs, TIMPs or altered ratios between them can be used as biomarkers of respiratory disease. We hypothesized that levels of MMPs, TIMPs and their ratios correlate with improvement in clinical findings and bronchoalveolar lavage fluid (BALF) cytology after 10 days of inhalative glucocorticoid therapy and environmental dust reduction (EDR) and may be used to monitor treatment success. Ten horses with a history of RAO participated in a prospective clinical study. Clinical and cytological scoring was performed before and after inhalative therapy using budesonide (1500 μg BID over 10 days) and EDR (bedding of wood shavings and wet hay as roughage). Gelatin zymography was performed for qualitative and semi-quantitative evaluation of MMP-2 and MMP-9 in BALF supernatant, while fluorimetry was used to evaluate MMP-8 activity. Additionally, specific equine ELISA assays were used for quantitative assessment of MMP-2, MMP-9, TIMP-1 and TIMP-2.
  
  
  RESULTS
  A significant reduction in the total and several single parameters of the clinical score were found after 10 days of inhalative therapy and EDR. The concentrations of MMP-2, MMP-9, TIMP-1 and TIMP-2 (ELISA) as well as their activities (MMP-2 and MMP-9 zymography and MMP-8 fluorimetry) were significantly decreased after therapy. Significant improvements in MMP-8/TIMP-1 and MMP-8/TIMP-2 ratios were also found, differences between other ratios before and after therapy were insignificant.
  
  
  CONCLUSIONS
  Metalloproteinases and their inhibitors, in particular MMP-9 and TIMP-2, are valuable markers for clinical improvement in RAO.
authors.affiliation: Equine Clinic, Freie Universitaet Berlin, Oertzenweg 19b, Berlin, 10163, Germany. Ann-Kristin.Barton@fu-berlin.de.
authors.forename: Ann Kristin
authors.identifier: http://orcid.org/0000-0002-3333-9647
authors.initials: AK
authors.lastname: Barton
authors.affiliation: Equine Clinic, Freie Universitaet Berlin, Oertzenweg 19b, Berlin, 10163, Germany.
authors.forename: Tarek
authors.initials: T
authors.lastname: Shety
authors.affiliation: Institute of Veterinary Biochemistry, Freie Universitaet Berlin, Oertzenweg 19b, Berlin, 10163, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Bondzio
authors.affiliation: Institute of Veterinary Biochemistry, Freie Universitaet Berlin, Oertzenweg 19b, Berlin, 10163, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Einspanier
authors.affiliation: Equine Clinic, Freie Universitaet Berlin, Oertzenweg 19b, Berlin, 10163, Germany.
authors.forename: Heidrun
authors.initials: H
authors.lastname: Gehlen
mesh_terms: D000280:Administration, Inhalation; D000402:Airway Obstruction / Q000175:diagnosis / Q000188:drug therapy / Q000201:enzymology / Q000662:veterinary*; D000818:Animals; D015415:Biomarkers; D004391:Dust; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D006734:Horse Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000201:enzymology*; D006736:Horses; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors / Q000627:therapeutic use*; D020782:Matrix Metalloproteinases / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D004391:Dust; D005938:Glucocorticoids; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases
keywords: Horse; Inflammatory marker; Lung; Metalloproteinases; Recurrent airway obstruction; Tissue inhibitors of metalloproteinases