Role of matrix metalloproteinases (MMPs) in cystic fibrosis

  • Stéphane Jouneau
  • Guillaume Léveiller
  • Sylvie Caulet-Maugendre
  • Graziella Brinchault
  • Chantal Belleguic
  • Benoît Desrues
  • Vincent Lagente
Part of the Progress in Inflammation Research book series (PIR)


Cystic fibrosis (CF) is the most frequent hereditary lethal disease in Caucasians. It is the consequence of a mutation in a chloride channel called CFTR. This defective channel leads to viscous secretions in all exocrine glands and therefore destruction and fibrosis of these organs. The main point of CF is the lung disease with inflammation and infection leading towards remodelling. There are only symptomatic treatments. Matrix metalloproteinases (MMPs) play several roles in CF development. Indeed, MMPs are involved in the regulation of CFTR channel. The alveolar levels of MMPs in CF patients are increased compared to controls with active form and lead to an imbalance between proteases and anti-proteases. MMPs are enhanced in sputum and plasma in severe CF patients. MMPs also have a role in regeneration of human CF airway surface epithelium and differentiation. MMPs could also interfere with the aerosolised medication. Together, these data exhibit the major role of MMPs in CF.


Cystic Fibrosis Cystic Fibrosis Transmembrane Conductance Regulator Force Vital Capacity Respir Crit Cystic Fibrosis Lung 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Quinton PM (1999) Physiological basis of cystic fibrosis: a historical perspective. Physiol Rev 79(1 Suppl): S3–S22PubMedGoogle Scholar
  2. 2.
    Barasch J, Kiss B, Prince A, Saiman L, Gruenert D, al-Awqati Q (1991) Defective acidification of intracellular organelles in cystic fibrosis. Nature 352(6330): 70–73PubMedCrossRefGoogle Scholar
  3. 3.
    Hasegawa H, Skach W, Baker O, Calayag MC, Lingappa V, Verkman AS (1992) A multifunctional aqueous channel formed by CFTR. Science 258(5087): 1477–1479PubMedCrossRefGoogle Scholar
  4. 4.
    Loussouarn G, Demolombe S, Mohammad-Panah R, Escande D, Baro I (1996) Expression of CFTR controls cAMP-dependent activation of epithelial K+ currents. Am J Physiol 271(5 Pt 1): C1565–C1573PubMedGoogle Scholar
  5. 5.
    Pilewski JM, Frizzell RA (1999) Role of CFTR in airway disease. Physiol Rev 79(1 Suppl): S215–S255PubMedGoogle Scholar
  6. 6.
    Stutts MJ, Canessa CM, Olsen JC, Hamrick M, Cohn JA, Rossier BC, Boucher RC (1995) CFTR as a cAMP-dependent regulator of sodium channels. Science 269(5225): 847–850PubMedCrossRefGoogle Scholar
  7. 7.
    Brasfield D, Hicks G, Soong S, Tiller RE (1979) The chest roentgenogram in cystic fibrosis: a new scoring system. Pediatrics 63(1): 24–29PubMedGoogle Scholar
  8. 8.
    Brasfield D, Hicks G, Soong S, Peters J, Tiller R (1980) Evaluation of scoring system of the chest radiograph in cystic fibrosis: a collaborative study. AJR Am J Roentgenol 134(6): 1195–1198PubMedGoogle Scholar
  9. 9.
    Shwachman H, Kulczycki LL (1958) Long-term study of one hundred five patients with cystic fibrosis; studies made over a five-to fourteen-year period. AMA J Dis Child 96(1): 6–15PubMedGoogle Scholar
  10. 10.
    Comeau AM, Accurso FJ, White TB, Campbell PW III, Hoffman G, Parad RB, Wilfond BS, Rosenfeld M, Sontag MK, Massie J et al (2007) Guidelines for implementation of cystic fibrosis newborn screening programs: Cystic Fibrosis Foundation workshop report. Pediatrics 119(2): e495–e518PubMedCrossRefGoogle Scholar
  11. 11.
    Wagener JS, Headley AA (2003) Cystic fibrosis: current trends in respiratory care. Respir Care 48(3): 234–245PubMedGoogle Scholar
  12. 12.
    Littlewood JM, Wolfe SP, Conway SP (2006) Diagnosis and treatment of intestinal malabsorption in cystic fibrosis. Pediatr Pulmonol 41(1): 35–49PubMedCrossRefGoogle Scholar
  13. 13.
    Derelle J (2003) Airway inflammation in cystic fibrosis. Rev Prat 53(2): 141–144PubMedGoogle Scholar
  14. 14.
    Khan TZ, Wagener JS, Bost T, Martinez J, Accurso FJ, Riches DW (1995) Early pulmonary inflammation in infants with cystic fibrosis. Am J Respir Crit Care Med 151(4): 1075–1082PubMedGoogle Scholar
  15. 15.
    De Rose V (2002) Mechanisms and markers of airway inflammation in cystic fibrosis. Eur Respir J 19(2): 333–340PubMedCrossRefGoogle Scholar
  16. 16.
    Birrer P, McElvaney NG, Rudeberg A, Sommer CW, Liechti-Gallati S, Kraemer R, Hubbard R, Crystal RG (1994) Protease-antiprotease imbalance in the lungs of children with cystic fibrosis. Am J Respir Crit Care Med 150(1): 207–213PubMedGoogle Scholar
  17. 17.
    Infeld MD (1997) Cell-matrix interactions in gland development in the lung. Exp Lung Res 23(2): 161–169PubMedCrossRefGoogle Scholar
  18. 18.
    Duszyk M, Shu Y, Sawicki G, Radomski A, Man SF, Radomski MW (1999) Inhibition of matrix metalloproteinase MMP-2 activates chloride current in human airway epithelial cells. Can J Physiol Pharmacol 77(7): 529–535PubMedCrossRefGoogle Scholar
  19. 19.
    Ratjen F, Hartog CM, Paul K, Wermelt J, Braun J (2002) Matrix metalloproteases in BAL fluid of patients with cystic fibrosis and their modulation by treatment with dornase alpha. Thorax 57(11): 930–934PubMedCrossRefGoogle Scholar
  20. 20.
    Delacourt C, Le BM, d’Ortho MP, Doit C, Scheinmann P, Navarro J, Harf A, Hartmann DJ, Lafuma C (1995) Imbalance between 95 kDa type IV collagenase and tissue inhibitor of metalloproteinases in sputum of patients with cystic fibrosis. Am J Respir Crit Care Med 152(2): 765–774PubMedGoogle Scholar
  21. 21.
    Gaggar A, Li Y, Weathington N, Winkler M, Kong M, Jackson P, Blalock JE, Clancy J (2007) Matrix metalloprotease-9 dysregulation in lower airway secretions of cystic fibrosis patients. Am J Physiol Lung Cell Mol Physiol 293: L96–L104PubMedCrossRefGoogle Scholar
  22. 22.
    Power C, O’Connor CM, MacFarlane D, O’Mahoney S, Gaffney K, Hayes J, FitzGerald MX (1994) Neutrophil collagenase in sputum from patients with cystic fibrosis. Am J Respir Crit Care Med 150(3): 818–822PubMedGoogle Scholar
  23. 23.
    Sagel SD, Kapsner RK, Osberg I (2005) Induced sputum matrix metalloproteinase-9 correlates with lung function and airway inflammation in children with cystic fibrosis. Pediatr Pulmonol 39(3): 224–232PubMedCrossRefGoogle Scholar
  24. 24.
    Jouneau S, Leveiller G, Desrues B, Lagente V, Martin-Chouly C (2005) Increased EMMPRIN and MT1-MMP levels in the plasma of the stable adult patients with cystic fibrosis. Eur Respir J 26(Suppl 49): 404sGoogle Scholar
  25. 25.
    Puchelle E, Le SP, Hajj R, Coraux C (2006) Regeneration of injured airway epithelium. Ann Pharm Fr 64(2): 107–113PubMedGoogle Scholar
  26. 26.
    Hajj R, Lesimple P, Nawrocki-Raby B, Birembaut P, Puchelle E, Coraux C (2007) Human airway surface epithelial regeneration is delayed and abnormal in cystic fibrosis. J Pathol 211(3): 340–350PubMedCrossRefGoogle Scholar
  27. 27.
    Attucci S, Gauthier A, Korkmaz B, Delepine P, Martino MF, Saudubray F, Diot P, Gauthier F (2006) EPI-hNE4, a proteolysis-resistant inhibitor of human neutrophil elastase and potential anti-inflammatory drug for treating cystic fibrosis. J Pharmacol Exp Ther 318(2): 803–809PubMedCrossRefGoogle Scholar

Copyright information

© Birkhäuser Verlag Basel/Switzerland 2008

Authors and Affiliations

  • Stéphane Jouneau
    • 1
    • 2
  • Guillaume Léveiller
    • 1
  • Sylvie Caulet-Maugendre
    • 3
  • Graziella Brinchault
    • 1
  • Chantal Belleguic
    • 1
  • Benoît Desrues
    • 1
  • Vincent Lagente
    • 2
  1. 1.Respiratory Medicine DepartmentPontchaillou HospitalRennesFrance
  2. 2.INSERM U620, Faculté de PharmacieUniversité de Rennes 1RennesFrance
  3. 3.Pathology DepartmentPontchaillou HospitalRennesFrance

Personalised recommendations