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BMC veterinary research2016; 12(1); 282; doi: 10.1186/s12917-016-0915-1

Metalloproteinases and their inhibitors are influenced by inhalative glucocorticoid therapy in combination with environmental dust reduction in equine recurrent airway obstruction.

Abstract: 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.
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Publication Date: 2016-12-09 PubMed ID: 27938355PubMed Central: PMC5148864DOI: 10.1186/s12917-016-0915-1Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research paper focuses on how inhalative glucocorticoid therapy, coupled with reducing environmental dust, impacts metalloproteinases and their inhibitors in horses suffering from recurrent airway obstruction (RAO). Results reveal that these factors, especially MMP-9 and TIMP-2, may be helpful biomarkers for clinical improvement in RAO.

Study Background

  • This research is founded on the understanding that overexpression of matrix-metalloproteinases (MMPs) can trigger tissue damage in equine recurrent airway obstruction (RAO). This happens when the balance with their natural inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), becomes offset.
  • When MMPs, TIMPs, or the relationship between them increase, they can be utilized to signal respiratory disease. The researchers hypothesized that the levels of MMPs, TIMPs, and their ratios could be indicators of enhanced clinical symptoms and bronchoalveolar lavage fluid (BALF) cytology following 10 days of inhalative glucocorticoid therapy and environmental dust reduction (EDR).

Methodology

  • Ten horses with a history of RAO participated in this prospective clinical study.
  • Clinical and cytological scoring was executed before and after inhalative therapy using budesonide along with EDR.
  • Gelatin zymography was used to evaluate MMP-2 and MMP-9 in BALF supernatant qualitatively and semi-quantitatively.
  • Fluorimetry was used to assess MMP-8 activity.
  • ELISA assays were used for quantitative evaluation of MMP-2, MMP-9, TIMP-1, and TIMP-2.

Findings

  • Significant reduction in the total and several individual parameters of the clinical score were found following 10 days of the inhalative therapy and EDR.
  • The levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 as well as their activities were remarkably lowered after the therapy.
  • Noteworthy improvements in MMP-8/TIMP-1 and MMP-8/TIMP-2 ratios were also observed, however, distinctions between other ratios before and after therapy were insignificant.

Conclusion

  • The study concludes that metalloproteinases and their inhibitors, specifically MMP-9 and TIMP-2, are crucial markers for clinical improvement in cases of RAO.

Cite This Article

APA
Barton AK, Shety T, Bondzio A, Einspanier R, Gehlen H. (2016). Metalloproteinases and their inhibitors are influenced by inhalative glucocorticoid therapy in combination with environmental dust reduction in equine recurrent airway obstruction. BMC Vet Res, 12(1), 282. https://doi.org/10.1186/s12917-016-0915-1

Publication

BMC veterinary research
ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 12
Issue: 1
Pages: 282
PII: 282

Researcher Affiliations

Barton, Ann Kristin
  • Equine Clinic, Freie Universitaet Berlin, Oertzenweg 19b, Berlin, 10163, Germany. Ann-Kristin.Barton@fu-berlin.de.
Shety, Tarek
  • Equine Clinic, Freie Universitaet Berlin, Oertzenweg 19b, Berlin, 10163, Germany.
Bondzio, Angelika
  • Institute of Veterinary Biochemistry, Freie Universitaet Berlin, Oertzenweg 19b, Berlin, 10163, Germany.
Einspanier, Ralf
  • Institute of Veterinary Biochemistry, Freie Universitaet Berlin, Oertzenweg 19b, Berlin, 10163, Germany.
Gehlen, Heidrun
  • Equine Clinic, Freie Universitaet Berlin, Oertzenweg 19b, Berlin, 10163, Germany.

MeSH Terms

  • Administration, Inhalation
  • Airway Obstruction / diagnosis
  • Airway Obstruction / drug therapy
  • Airway Obstruction / enzymology
  • Airway Obstruction / veterinary
  • Animals
  • Biomarkers
  • Dust
  • Female
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / pharmacology
  • Horse Diseases / diagnosis
  • Horse Diseases / drug therapy
  • Horse Diseases / enzymology
  • Horses
  • Male
  • Matrix Metalloproteinase Inhibitors / therapeutic use
  • Matrix Metalloproteinases / metabolism

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Citations

This article has been cited 6 times.
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