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Home / Equine Research Bank / Mediators Inflamm / Metalloproteinases and their Inhibitors under the Course of ...
Mediators of inflammation2019; 2019; 7845623; doi: 10.1155/2019/7845623

Metalloproteinases and their Inhibitors under the Course of Immunostimulation by CPG-ODN and Specific Antigen Inhalation in Equine Asthma.

Abstract: Inhalation of immunostimulatory bacterial DNA segments (cytosine-phosphate-guanosine-oligodeoxynucleotides, CpG-ODN) normalizes clinical and cytologic parameters in severe equine asthma. We hypothesized that CpG-ODN inhalation also reduces the misbalance of elastinolytic activity in asthmatic horses. Methods: Twenty asthmatic horses diagnosed by clinical examinations using a scoring system were included. All horses inhaled CpG-ODNs for 14 days in 2-day intervals. Matrix metalloproteinase (MMP-2/-9) and tissue inhibitors of metalloproteinase (TIMP-1/-2) concentrations were measured in tracheal aspirates using equine sandwich ELISAs before and 2 and 6 weeks after CpG-ODN inhalation. Results: MMP and TIMP concentrations correlated with the results of clinical scoring in all stages of equine asthma. Inhalation therapy led to significant reductions in clinical scores. MMP-2, MMP-9, and TIMP-2 concentrations were significantly reduced immediately, and all MMP and TIMP concentrations 6 weeks after therapy. Conclusions: In equine asthma, overexpression of MMPs contributes to pathological tissue destruction, while TIMPs counteract MMPs with overexpression leading to fibrosis formation. The results of this study show that CpG-ODN inhalation may be an effective therapy to address a misbalance in equine asthma. Conclusions: Misbalance of elastinolytic activity seems to improve by CpG-ODN inhalation for at least 6 weeks posttherapy, which may reduce the remodeling of the extracellular matrix. Further studies should evaluate this effect in comparison to glucocorticoid inhalation therapy. Conclusions: CpG-ODN inhalation may be an effective therapy in the prevention of pulmonary fibrosis formation in equine asthma.
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Publication Date: 2019-06-17 PubMed ID: 31316303PubMed Central: PMC6604421DOI: 10.1155/2019/7845623Google Scholar: Lookup
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  • Clinical Trial
  • Veterinary
  • Journal Article

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 article investigates how inhaling bacterial DNA segments (CpG-ODNs) can remedy the imbalance of proteins that break down and rebuild lung tissue in horses with severe asthma. It concludes that this treatment may be a viable option for preventing lung scarring.

Research Methodology

  • The study involved twenty horses diagnosed with asthma. These diagnoses were confirmed through clinical examinations using a scoring system for assessing the severity of the condition.
  • The treatment administered to all participating horses consisted of inhalation therapy using CpG-ODNs over a span of 14 days, with treatments given in 2-day intervals.
  • Pre-treatment and post-treatment evaluations measured the levels concentration of matrix metalloproteinases (MMP-2/-9) and tissue inhibitors of metalloproteinase (TIMP-1/-2) in tracheal aspirates. These are key proteins that respectively contribute towards the degradation and building up of lung tissue.

Key Findings

  • The concentrations of MMPs and TIMPs correlated with the clinical scoring results at all stages of equine asthma. An imbalance of these proteins contributes to the advancement of the disease.
  • Following the inhalation therapy, significant reductions were observed in both clinical asthma scores and the concentrations of MMPs and TIMPs.
  • The concentrations of MMP-2, MMP-9, and TIMP-2 showed marked reduction immediately after the therapy. All concentrations of MMPs and TIMPs were reduced at the 6-week follow-up.

Conclusions

  • The study concluded that an overexpression of MMPs, contributing to pathological tissue destruction, is countered by TIMPs, whose own overexpression can lead to fibrosis, or scarring of lung tissue. These imbalances appear to be improved by the administration of CpG-ODN inhalation therapy.
  • The endurance of the beneficial effects of the therapy with regard to the balances of MMPs and TIMPs was noted up to at least 6 weeks post-therapy. This may help reduce the remodeling of the extracellular matrix, thus contributing to better management of equine asthma.
  • The research suggests that CpG-ODN inhalation therapy may serve as an effective intervention in the prevention of pulmonary fibrosis formation in equine asthma. However, they recommend further studies to compare this effect with that of glucocorticoid inhalation therapy.

Cite This Article

APA
Barton AK, Shety T, Klier J, Geis S, Einspanier R, Gehlen H. (2019). Metalloproteinases and their Inhibitors under the Course of Immunostimulation by CPG-ODN and Specific Antigen Inhalation in Equine Asthma. Mediators Inflamm, 2019, 7845623. https://doi.org/10.1155/2019/7845623

Publication

Mediators of inflammation
ISSN: 1466-1861
NlmUniqueID: 9209001
Country: United States
Language: English
Volume: 2019
Pages: 7845623
PII: 7845623

Researcher Affiliations

Barton, Ann Kristin
  • Equine Clinic, Freie Universitaet Berlin, Germany.
Shety, Tarek
  • Equine Clinic, Freie Universitaet Berlin, Germany.
  • Animal Medicine Department, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
Klier, John
  • Centre for Clinical Veterinary Medicine, Equine Clinic, LMU Munich, Germany.
Geis, Sabine
  • Equine Clinic, Freie Universitaet Berlin, Germany.
  • Centre for Clinical Veterinary Medicine, Equine Clinic, LMU Munich, Germany.
Einspanier, Ralf
  • Institute of Veterinary Biochemistry, Freie Universitaet Berlin, Germany.
Gehlen, Heidrun
  • Equine Clinic, Freie Universitaet Berlin, Germany.

MeSH Terms

  • Administration, Inhalation
  • Animals
  • Asthma / immunology
  • Asthma / therapy
  • Asthma / veterinary
  • Extracellular Matrix / metabolism
  • Horse Diseases / immunology
  • Horse Diseases / therapy
  • Horses
  • Immunization
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinase Inhibitors / pharmacology
  • Metalloproteases / metabolism
  • Oligodeoxyribonucleotides / administration & dosage
  • Tissue Inhibitor of Metalloproteinase-1 / antagonists & inhibitors
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Tissue Inhibitor of Metalloproteinase-2 / antagonists & inhibitors
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism

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Citations

This article has been cited 3 times.
  1. Klier J, Fuchs S, Winter G, Gehlen H. Inhalative Nanoparticulate CpG Immunotherapy in Severe Equine Asthma: An Innovative Therapeutic Concept and Potential Animal Model for Human Asthma Treatment. Animals (Basel) 2022 Aug 16;12(16).
    doi: 10.3390/ani12162087pubmed: 36009677google scholar: lookup
  2. Simões J, Batista M, Tilley P. The Immune Mechanisms of Severe Equine Asthma-Current Understanding and What Is Missing. Animals (Basel) 2022 Mar 16;12(6).
    doi: 10.3390/ani12060744pubmed: 35327141google scholar: lookup
  3. Morales-Vázquez MM, Meza-Serrano E, Lara-Pereyra I, Acuña-González RJ, Alonso-Morales R, Hayen-Valles S, Boeta AM, Zarco L, Lozano-Cuenca J, López-Canales JS, Flores-Herrera H. Equine Placentitis in Mares Induces the Secretion of Pro-Inflammatory Cytokine eIL-1β and the Active Extracellular Matrix Metalloproteinase (MMP)-9. Vet Sci 2023 Aug 22;10(9).
    doi: 10.3390/vetsci10090532pubmed: 37756054google scholar: lookup
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