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Home / Equine Research Bank / Mediators Inflamm / Metalloproteinases and Their Tissue Inhibitors in Comparison...
Mediators of inflammation2015; 2015; 569512; doi: 10.1155/2015/569512

Metalloproteinases and Their Tissue Inhibitors in Comparison between Different Chronic Pneumopathies in the Horse.

Abstract: In chronic respiratory disease, matrix metalloproteinases (MMPs) contribute to pathological tissue destruction when expressed in excess, while tissue inhibitors of metalloproteinases (TIMPs) counteract MMPs with overexpression leading to fibrosis formation. They may be out of balance in equine pneumopathies and serve as biomarkers of pulmonary inflammation. We hypothesized that MMPs and TIMPs correlate to clinical findings and bronchoalveolar lavage fluid cytology in different equine chronic pneumopathies. Using a scoring system, 61 horses were classified controls as free of respiratory disease (n = 15), recurrent airway obstruction (RAO, n = 17), inflammatory airway disease (IAD, n = 18), or chronic interstitial pneumopathy (CIP, n = 11). Zymography and equine MMP and TIMP assays were used to detect MMP-2, MMP-8, MMP-9 as well as TIMP-1, and TIMP-2 in BALF supernatant. MMP-2, TIMP-1, and TIMP-2 concentrations were significantly increased in RAO and IAD compared to controls. MMP-9 concentration and MMP-8 activity evaluated by fluorimetry were significantly increased in RAO, IAD, and CIP. These results were confirmed by zymography for MMP-2 and MMP-9 activity in 52 horses. In conclusion, MMPs and TIMPs correlate well with clinical and cytologic findings. These findings support the usefulness of MMPs, TIMPs, and their ratios to evaluate the severity of respiratory disease and may help to identify subclinical cases.
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Publication Date: 2015-12-03 PubMed ID: 26770019PubMed Central: PMC4681803DOI: 10.1155/2015/569512Google Scholar: Lookup
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  • Comparative Study
  • 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.

This research explores the relationship between enzymes known as matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), in various equine chronic respiratory diseases. The study discovered that the balance between MMPs and TIMPs could be used to evaluate the severity of these diseases.

Research Background

  • Chronic respiratory diseases involve pathological tissue destruction, which is further enhanced by an excess of matrix metalloproteinases (MMPs).
  • On the other hand, tissue inhibitors of metalloproteinases (TIMPs) can counteract the effects of MMPs, but their overexpression may lead to the production of fibrosis.
  • In horses suffering from pneumopathies, or lung diseases, an imbalance between MMPs and TIMPs could occur and be used as markers for lung inflammation.

Study Hypotheses and Methodology

  • The study hypothesized that the occurrence of MMPs and TIMPs could correlate with clinical findings and the cytology of bronchoalveolar lavage fluid in horses affected by different chronic pneumopathies.
  • For the study, 61 horses were scored and divided into groups: those without respiratory disease (controls), those with recurrent airway obstruction (RAO), inflammatory airway disease (IAD), and chronic interstitial pneumopathy (CIP).
  • The study used zymography and equine MMP and TIMP assays to detect the MMP-2, MMP-8, and MMP-9 enzymes, as well as the TIMP-1 and TIMP-2 inhibitors in the bronchoalveolar lavage fluid (a fluid collected from the lungs) supernatant.

Study Findings

  • The study discovered that concentrations of MMP-2, TIMP-1, and TIMP-2 were significantly elevated in horses with RAO and IAD compared to the control group.
  • Also, MMP-9 concentration and MMP-8 activity were notably higher in the RAO, IAD, and CIP groups.
  • Horses with RAO, IAD, and CIP also showed higher activity of MMP-2 and MMP-9, which was confirmed using zymography on 52 of the horses.

Conclusion and Uses

  • The research concluded that there is a strong correlation between the levels of MMPs and TIMPs and the clinical and cytologic findings in horses with chronic respiratory diseases.
  • The study suggests that MMPs, TIMPs, and their ratios could be useful in assessing the severity of respiratory disease in horses, and may even help in identifying subclinical cases, i.e., cases where symptoms are not yet present or are too mild to be detected using normal examination methods.

Cite This Article

APA
Barton AK, Shety T, Bondzio A, Einspanier R, Gehlen H. (2015). Metalloproteinases and Their Tissue Inhibitors in Comparison between Different Chronic Pneumopathies in the Horse. Mediators Inflamm, 2015, 569512. https://doi.org/10.1155/2015/569512

Publication

Mediators of inflammation
ISSN: 1466-1861
NlmUniqueID: 9209001
Country: United States
Language: English
Volume: 2015
Pages: 569512
PII: 569512

Researcher Affiliations

Barton, Ann Kristin
  • Equine Clinic, Veterinary Faculty, Freie Universitaet Berlin, Oertzenweg 19b, 14163 Berlin, Germany.
Shety, Tarek
  • Equine Clinic, Veterinary Faculty, Freie Universitaet Berlin, Oertzenweg 19b, 14163 Berlin, Germany.
Bondzio, Angelika
  • Institute of Veterinary Biochemistry, Veterinary Faculty, Freie Universitaet Berlin, Oertzenweg 19b, 14163 Berlin, Germany.
Einspanier, Ralf
  • Institute of Veterinary Biochemistry, Veterinary Faculty, Freie Universitaet Berlin, Oertzenweg 19b, 14163 Berlin, Germany.
Gehlen, Heidrun
  • Equine Clinic, Veterinary Faculty, Freie Universitaet Berlin, Oertzenweg 19b, 14163 Berlin, Germany.

MeSH Terms

  • Animals
  • Bronchoalveolar Lavage Fluid / cytology
  • Chronic Disease
  • Enzyme-Linked Immunosorbent Assay
  • Horse Diseases / metabolism
  • Horses
  • Lung / physiopathology
  • Lung Diseases / metabolism
  • Lung Diseases / veterinary
  • Matrix Metalloproteinases / metabolism
  • Severity of Illness Index
  • Tissue Inhibitor of Metalloproteinases / analysis

References

This article includes 52 references
  1. Clutterbuck AL, Harris P, Allaway D, Mobasheri A. Matrix metalloproteinases in inflammatory pathologies of the horse.. Vet J 2010 Jan;183(1):27-38.
    doi: 10.1016/j.tvjl.2008.09.022pubmed: 19022687google scholar: lookup
  2. Lu P, Takai K, Weaver VM, Werb Z. Extracellular matrix degradation and remodeling in development and disease.. Cold Spring Harb Perspect Biol 2011 Dec 1;3(12).
    doi: 10.1101/cshperspect.a005058pmc: PMC3225943pubmed: 21917992google scholar: lookup
  3. Tayebjee M H, Lip G Y H. Matrix metalloproteinases and the extracellular matrix. .
  4. McCawley LJ, Matrisian LM. Matrix metalloproteinases: they're not just for matrix anymore!. Curr Opin Cell Biol 2001 Oct;13(5):534-40.
    doi: 10.1016/s0955-0674(00)00248-9pubmed: 11544020google scholar: lookup
  5. Frantz C, Stewart KM, Weaver VM. The extracellular matrix at a glance.. J Cell Sci 2010 Dec 15;123(Pt 24):4195-200.
    doi: 10.1242/jcs.023820pmc: PMC2995612pubmed: 21123617google scholar: lookup
  6. Chapman HA. Disorders of lung matrix remodeling.. J Clin Invest 2004 Jan;113(2):148-57.
    doi: 10.1172/jci200420729pmc: PMC311438pubmed: 14722604google scholar: lookup
  7. Manicone AM, McGuire JK. Matrix metalloproteinases as modulators of inflammation.. Semin Cell Dev Biol 2008 Feb;19(1):34-41.
    doi: 10.1016/j.semcdb.2007.07.003pmc: PMC2235912pubmed: 17707664google scholar: lookup
  8. Gaggar A, Jackson PL, Noerager BD, O'Reilly PJ, McQuaid DB, Rowe SM, Clancy JP, Blalock JE. A novel proteolytic cascade generates an extracellular matrix-derived chemoattractant in chronic neutrophilic inflammation.. J Immunol 2008 Apr 15;180(8):5662-9.
    doi: 10.4049/jimmunol.180.8.5662pmc: PMC3998665pubmed: 18390751google scholar: lookup
  9. Everts V, Buttle DJ. Methods in studying ECM degradation.. Methods 2008 May;45(1):86-92.
    doi: 10.1016/j.ymeth.2008.01.009pubmed: 18442708google scholar: lookup
  10. Lavoie J P. Recurrent airway obstruction (heaves) and summer-pasture-associated obstructive pulmonary disease. .
  11. Lugo J, Harkema JR, deFeijter-Rupp H, Bartner L, Boruta D, Robinson NE. Airway inflammation is associated with mucous cell metaplasia and increased intraepithelial stored mucosubstances in horses.. Vet J 2006 Sep;172(2):293-301.
    doi: 10.1016/j.tvjl.2005.04.018pubmed: 15925524google scholar: lookup
  12. GROSS J, LAPIERE CM. Collagenolytic activity in amphibian tissues: a tissue culture assay.. Proc Natl Acad Sci U S A 1962 Jun 15;48(6):1014-22.
    doi: 10.1073/pnas.48.6.1014pmc: PMC220898pubmed: 13902219google scholar: lookup
  13. Koivunen AL, Maisi P, Konttinen YT, Prikk K, Sandholm M. Collagenolytic activity and its sensitivity to doxycycline inhibition in tracheal aspirates of horses with chronic obstructive pulmonary disease.. Acta Vet Scand 1997;38(1):9-16.
    pmc: PMC8057019pubmed: 9129342doi: 10.1186/bf03548503google scholar: lookup
  14. Raulo SM, Sorsa TA, Kiili MT, Maisi PS. Evaluation of collagenase activity, matrix metalloproteinase-8, and matrix metalloproteinase-13 in horses with chronic obstructive pulmonary disease.. Am J Vet Res 2001 Jul;62(7):1142-8.
    doi: 10.2460/ajvr.2001.62.1142pubmed: 11453493google scholar: lookup
  15. Raulo SM, Sorsa TA, Maisi PS. Concentrations of elastinolytic metalloproteinases in respiratory tract secretions of healthy horses and horses with chronic obstructive pulmonary disease.. Am J Vet Res 2000 Sep;61(9):1067-73.
    doi: 10.2460/ajvr.2000.61.1067pubmed: 10976738google scholar: lookup
  16. Koivunen AL, Maisi P, Konttinen YT, Sandholm M. Gelatinolytic activity in tracheal aspirates of horses with chronic obstructive pulmonary disease.. Acta Vet Scand 1997;38(1):17-27.
    pmc: PMC8057023pubmed: 9129343doi: 10.1186/bf03548504google scholar: lookup
  17. Raulo SM, Sorsa T, Tervahartiala T, Pirilä E, Maisi P. MMP-9 as a marker of inflammation in tracheal epithelial lining fluid (TELF) and in bronchoalveolar fluid (BALF) of COPD horses.. Equine Vet J 2001 Mar;33(2):128-36.
    doi: 10.1111/j.2042-3306.2001.tb05375.xpubmed: 11266061google scholar: lookup
  18. Maisi P, Sorsa T, Raulo SM, Prikk K, Sepper R, McGorum B. Increased matrix metalloproteinase (MMP)-9 in the airway after allergen challenge.. Am J Respir Crit Care Med 2001 Nov 1;164(9):1740; discussion 1740-1.
    pubmed: 11719319doi: 10.1164/ajrccm.164.9.correspondence_bgoogle scholar: lookup
  19. Nevalainen M, Raulo SM, Brazil TJ, Pirie RS, Sorsa T, McGorum BC, Maisi P. Inhalation of organic dusts and lipopolysaccharide increases gelatinolytic matrix metalloproteinases (MMPs) in the lungs of heaves horses.. Equine Vet J 2002 Mar;34(2):150-5.
    pubmed: 11902757doi: 10.2746/042516402776767277google scholar: lookup
  20. Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry.. Circ Res 2003 May 2;92(8):827-39.
    doi: 10.1161/01.res.0000070112.80711.3dpubmed: 12730128google scholar: lookup
  21. Will H, Atkinson SJ, Butler GS, Smith B, Murphy G. The soluble catalytic domain of membrane type 1 matrix metalloproteinase cleaves the propeptide of progelatinase A and initiates autoproteolytic activation. Regulation by TIMP-2 and TIMP-3.. J Biol Chem 1996 Jul 19;271(29):17119-23.
    doi: 10.1074/jbc.271.29.17119pubmed: 8663332google scholar: lookup
  22. D'Armiento JM, Goldklang MP, Hardigan AA, Geraghty P, Roth MD, Connett JE, Wise RA, Sciurba FC, Scharf SM, Thankachen J, Islam M, Ghio AJ, Foronjy RF. Increased matrix metalloproteinase (MMPs) levels do not predict disease severity or progression in emphysema.. PLoS One 2013;8(2):e56352.
    doi: 10.1371/journal.pone.0056352pmc: PMC3575373pubmed: 23441181google scholar: lookup
  23. Mattos W, Lim S, Russell R, Jatakanon A, Chung KF, Barnes PJ. Matrix metalloproteinase-9 expression in asthma: effect of asthma severity, allergen challenge, and inhaled corticosteroids.. Chest 2002 Nov;122(5):1543-52.
    doi: 10.1378/chest.122.5.1543pubmed: 12426251google scholar: lookup
  24. Matsumoto H, Niimi A, Takemura M, Ueda T, Minakuchi M, Tabuena R, Chin K, Mio T, Ito Y, Muro S, Hirai T, Morita S, Fukuhara S, Mishima M. Relationship of airway wall thickening to an imbalance between matrix metalloproteinase-9 and its inhibitor in asthma.. Thorax 2005 Apr;60(4):277-81.
    doi: 10.1136/thx.2004.028936pmc: PMC1747359pubmed: 15790981google scholar: lookup
  25. Kumagai K, Ohno I, Okada S, Ohkawara Y, Suzuki K, Shinya T, Nagase H, Iwata K, Shirato K. Inhibition of matrix metalloproteinases prevents allergen-induced airway inflammation in a murine model of asthma.. J Immunol 1999 Apr 1;162(7):4212-9.
    pubmed: 10201949
  26. Ohnesorge B, Trötschel C, Deegen E. Diagnostic value of capnography in horses with RAO. Proceedings of the 5th World Equine Vet Assoc Congress 1998; pp. 65–69.
  27. Gehlen H, Oey L, Rohn K, Bilzer T, Stadler P. Pulmonary dysfunction and skeletal muscle changes in horses with RAO.. J Vet Intern Med 2008 Jul-Aug;22(4):1014-21.
    doi: 10.1111/j.1939-1676.2008.0111.xpubmed: 18498323google scholar: lookup
  28. Robinson NE. International Workshop on Equine Chronic Airway Disease. Michigan State University 16-18 June 2000.. Equine Vet J 2001 Jan;33(1):5-19.
    doi: 10.2746/042516401776767412pubmed: 11191611google scholar: lookup
  29. Couëtil LL, Hoffman AM, Hodgson J, Buechner-Maxwell V, Viel L, Wood JL, Lavoie JP. Inflammatory airway disease of horses.. J Vet Intern Med 2007 Mar-Apr;21(2):356-61.
    pubmed: 17427403doi: 10.1892/0891-6640(2007)21[356:iadoh]2.0.co;2google scholar: lookup
  30. Dieckmann M P, Klein H J, Deegen E. Chronic interstitial lung disease in the horse—findings in arterial bloodgas analysis, tracheobronchial mucus cytology and radiological examination of the thorax. Pferdeheilkunde 1990;6:155–160.
  31. Hu X, Beeton C. Detection of functional matrix metalloproteinases by zymography.. J Vis Exp 2010 Nov 8;(45).
    doi: 10.3791/2445pmc: PMC3159606pubmed: 21085107google scholar: lookup
  32. Chung M K. Correlation coefficient. .
  33. Dieckmann M, Deegen E. Clinical aspect of tracheobronchial aspirates cytology. Pferdeheilkunde 1990;6:101–110.
  34. Gerber V, Straub R, Marti E, Hauptman J, Herholz C, King M, Imhof A, Tahon L, Robinson NE. Endoscopic scoring of mucus quantity and quality: observer and horse variance and relationship to inflammation, mucus viscoelasticity and volume.. Equine Vet J 2004 Nov;36(7):576-82.
    pubmed: 15581321doi: 10.2746/0425164044864525google scholar: lookup
  35. Simonen-Jokinen T, Pirie RS, McGorum BC, Maisi P. Effect of composition and different fractions of hay dust suspension on inflammation in lungs of heaves-affected horses: MMP-9 and MMP-2 as indicators of tissue destruction.. Equine Vet J 2005 Sep;37(5):412-7.
    pubmed: 16163942doi: 10.2746/042516405774480111google scholar: lookup
  36. Simonen-Jokinen T, Pirie RS, McGorum B, Maisi P. Dose responses to inhalation of endotoxin, hay dust suspension and Aspergillus fumigatus extract in horses as measured by levels and activation of matrix metalloproteinase-9.. Equine Vet J 2005 Mar;37(2):155-60.
    pubmed: 15779629doi: 10.2746/0425164054223796google scholar: lookup
  37. Sepper R, Konttinen YT, Ding Y, Takagi M, Sorsa T. Human neutrophil collagenase (MMP-8), identified in bronchiectasis BAL fluid, correlates with severity of disease.. Chest 1995 Jun;107(6):1641-7.
    doi: 10.1378/chest.107.6.1641pubmed: 7781360google scholar: lookup
  38. Finlay GA, Russell KJ, McMahon KJ, D'arcy EM, Masterson JB, FitzGerald MX, O'Connor CM. Elevated levels of matrix metalloproteinases in bronchoalveolar lavage fluid of emphysematous patients.. Thorax 1997 Jun;52(6):502-6.
    doi: 10.1136/thx.52.6.502pmc: PMC1758576pubmed: 9227714google scholar: lookup
  39. Gueders MM, Foidart JM, Noel A, Cataldo DD. Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs in the respiratory tract: potential implications in asthma and other lung diseases.. Eur J Pharmacol 2006 Mar 8;533(1-3):133-44.
    doi: 10.1016/j.ejphar.2005.12.082pubmed: 16487964google scholar: lookup
  40. Demedts IK, Brusselle GG, Bracke KR, Vermaelen KY, Pauwels RA. Matrix metalloproteinases in asthma and COPD.. Curr Opin Pharmacol 2005 Jun;5(3):257-63.
    doi: 10.1016/j.coph.2004.12.005pubmed: 15907912google scholar: lookup
  41. Lee YC, Lee HB, Rhee YK, Song CH. The involvement of matrix metalloproteinase-9 in airway inflammation of patients with acute asthma.. Clin Exp Allergy 2001 Oct;31(10):1623-30.
    doi: 10.1046/j.1365-2222.2001.01211.xpubmed: 11678864google scholar: lookup
  42. Cataldo DD, Bettiol J, Noël A, Bartsch P, Foidart JM, Louis R. Matrix metalloproteinase-9, but not tissue inhibitor of matrix metalloproteinase-1, increases in the sputum from allergic asthmatic patients after allergen challenge.. Chest 2002 Nov;122(5):1553-9.
    doi: 10.1378/chest.122.5.1553pubmed: 12426252google scholar: lookup
  43. Castano R, Miedinger D, Maghni K, Ghezzo H, Trudeau C, Castellanos L, Wattiez M, Vandenplas O, Malo JL. Matrix metalloproteinase-9 increases in the sputum from allergic occupational asthma patients after specific inhalation challenge.. Int Arch Allergy Immunol 2013;160(2):161-4.
    doi: 10.1159/000339737pubmed: 23018543google scholar: lookup
  44. Belleguic C, Corbel M, Germain N, Léna H, Boichot E, Delaval PH, Lagente V. Increased release of matrix metalloproteinase-9 in the plasma of acute severe asthmatic patients.. Clin Exp Allergy 2002 Feb;32(2):217-23.
    doi: 10.1046/j.1365-2222.2002.01219.xpubmed: 11929485google scholar: lookup
  45. Ohnishi K, Takagi M, Kurokawa Y, Satomi S, Konttinen YT. Matrix metalloproteinase-mediated extracellular matrix protein degradation in human pulmonary emphysema.. Lab Invest 1998 Sep;78(9):1077-87.
    pubmed: 9759652
  46. Cataldo D, Munaut C, Noël A, Frankenne F, Bartsch P, Foidart JM, Louis R. MMP-2- and MMP-9-linked gelatinolytic activity in the sputum from patients with asthma and chronic obstructive pulmonary disease.. Int Arch Allergy Immunol 2000 Nov;123(3):259-67.
    doi: 10.1159/000024452pubmed: 11112863google scholar: lookup
  47. Vignola AM, Riccobono L, Mirabella A, Profita M, Chanez P, Bellia V, Mautino G, D'accardi P, Bousquet J, Bonsignore G. Sputum metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio correlates with airflow obstruction in asthma and chronic bronchitis.. Am J Respir Crit Care Med 1998 Dec;158(6):1945-50.
    doi: 10.1164/ajrccm.158.6.9803014pubmed: 9847290google scholar: lookup
  48. Betsuyaku T, Nishimura M, Takeyabu K, Tanino M, Venge P, Xu S, Kawakami Y. Neutrophil granule proteins in bronchoalveolar lavage fluid from subjects with subclinical emphysema.. Am J Respir Crit Care Med 1999 Jun;159(6):1985-91.
    doi: 10.1164/ajrccm.159.6.9809043pubmed: 10351949google scholar: lookup
  49. Donaldson MT, Beech J, Ennulat D, Hamir AN. Interstitial pneumonia and pulmonary fibrosis in a horse.. Equine Vet J 1998 Mar;30(2):173-5.
    doi: 10.1111/j.2042-3306.1998.tb04480.xpubmed: 9535077google scholar: lookup
  50. Venner M, Schmidbauer S, Drommer W, Deegen E. Percutaneous lung biopsy in the horse: comparison of two instruments and repeated biopsy in horses with induced acute interstitial pneumopathy.. J Vet Intern Med 2006 Jul-Aug;20(4):968-73.
    doi: 10.1892/0891-6640(2006)20[968:plbith]2.0.co;2pubmed: 16955824google scholar: lookup
  51. Tilley P, Sales Luis JP, Branco Ferreira M. Correlation and discriminant analysis between clinical, endoscopic, thoracic X-ray and bronchoalveolar lavage fluid cytology scores, for staging horses with recurrent airway obstruction (RAO).. Res Vet Sci 2012 Oct;93(2):1006-14.
    doi: 10.1016/j.rvsc.2011.10.024pubmed: 22136797google scholar: lookup
  52. Mazan MR, Vin R, Hoffman AM. Radiographic scoring lacks predictive value in inflammatory airway disease.. Equine Vet J 2005 Nov;37(6):541-5.
    pubmed: 16295932doi: 10.2746/042516405775314899google scholar: lookup

Citations

This article has been cited 16 times.
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