Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1 (5-Year IF – 2.0)
Journal Citation Indicator (JCI) (2023) – 0.4
Scopus CiteScore – 3.7 (CiteScore Tracker 3.3)
Index Copernicus  – 161.11; MNiSW – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2007, vol. 16, nr 3, May-June, p. 417–423

Publication type: review article

Language: English

Metalloproteinases and Airway Remodeling in Asthma

Metaloproteinazy a remodeling w astmie oskrzelowej

Maria Kraus−Filarska1,, Magdalena Kosińska1,, Aneta Tomkowicz1,

1 Department of Internal Medicine and Allergology Silesian Piasts University of Medicine in Wrocław, Poland

Abstract

Asthma is a chronic inflammatory disease of the airways. The term “airway remodeling” has been applied to structural changes observed in asthmatic airways. Among other effects, this includes alterations in the extracellular matrix due to connective tissue cell dysfunction. Matrix metalloproteinases (MMPs) are key regulators of extracellular matrix composition. MMPs are a group of enzymes (endopeptidases) which participate in the degradation of almost all extracellular matrix protein components. Tissue inhibitors of metalloproteinases (TIMPs) regulate the synthesis, secretion, and activity of MMPs. It is not clear which mechanisms are involved in the maintenance of the equilibrium between MMPs and TIMPs in the asthmatic airways. An excess of TIMPs could favor airways fibrosis and thus lead to airway remodeling. Further studies are needed to develop novel asthma therapies directed against appropriate targets within the extracellular matrix, as the currently available corticosteroid treatment have little impact on extracellular matrix homeostasis and airway remodeling.

Streszczenie

Astma oskrzelowa jest przewlekłą chorobą zapalną, w której dochodzi do rozwoju zmian strukturalnych w drogach oddechowych, określanych mianem przebudowy (remodelingu). Jednym z elementów przebudowy oskrzeli jest zmiana składu macierzy pozakomórkowej, która jest związana z zaburzoną czynnością komórek tkanki łącznej. Kluczową rolę w przemodelowaniu macierzy pozakomórkowej odgrywają metaloproteinazy macierzy (MMPs – matrix metalloproteinases). MMPs są grupą enzymów (endopeptydaz), które uczestniczą w trawieniu prawie wszystkich składników białkowych macierzy pozakomórkowej. Wytwarzanie, wydzielanie i aktywność MMPs są regulowane na poziomach transkrypcji, aktywacji i hamowania przez tkankowe inhibitory metaloproteinaz (TIMPs – tissue inhibitors of metalloproteinases). Mechanizmy odpowiedzialne za równowagę między MMPs i TIMPs w drogach oddechowych chorych na astmę nie zostały w pełni wyjaśnione. Zaburzenie równowagi układu MMPs/TIMPs na korzyść TIMPs może sprzyjać procesom włóknienia, a tym samym propagować przebudowę dróg oddechowych. Niezbędne są dalsze badania, które mogą przyczynić się do odkrycia nowych dróg w terapii astmy, tym bardziej że stosowane w leczeniu tej choroby glikokortykosteroidy jedynie w niewielkim stopniu wpływają na homeostazę składników macierzy pozakomórkowej oraz przebudowę dróg oddechowych.

Key words

asthma, remodeling, extracellular matrix, metalloproteinases, tissue inhibitors of metalloproteinases

Słowa kluczowe

astma, przebudowa, macierz pozakomórkowa, metaloproteinazy, tkankowe inhibitory metaloproteinaz

References (45)

  1. Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) 2006. Available from: http://www.ginasthma.org.
  2. Bousquet J, Jeffery PK, Busse WW, Johnsson M, Vignola AM: Asthma: From bronchoconstriction to airways inflammation and remodeling. Am J Respir Crit Care Med 2000, 161, 1720–1745.
  3. Elias JA, Zhu Z, Chupp G, Homer RJ: Airway remodeling in asthma. J Clin Invest 1999, 104, 1001–1006.
  4. McParland BE, Macklem PT, Pare PD: Airway wall remodeling: friend or foe? J Appl Physiol 2003, 95, 426–434.
  5. Visse R, Nagase H: Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 2003, 92, 827–839.
  6. Gueders MM, Foidart J−M, 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, 533, 133–144.
  7. Kelly EA, Jarjour NN: Role of matrix metalloproteinases in asthma. Curr Opin Pulm Med 2003, 9, 28–33.
  8. Clark IM, Morrison JJ, Hackett GA, Powell EK, Cawson TE, Smith SK: Tissue inhibitor of matrix metalloproteinases: serum levels during pregnancy and labor, term and preterm. Obstet Gynecol 1994, 83, 532–537.
  9. Beckett PA, Howarth PH: Pharmacotherapy and airway remodeling in asthma? Thorax 2003, 58, 163–174.
  10. Dollery CM, McEwan JR, Henney AM: Matrix metalloproteinases and cardiovascular disease. Circ Res 1995, 77, 863–868.
  11. Collette T, Bellehumeur C, Kats R, Maheux R, Mailloux J, Villeneuve M, Akoum A: Evidence for an increased release of proteolytic activity by the eutopic endometrial tissue in women with endometriosis and for involvement of MMP−9. Hum Reprod 2004, 19, 1257–1264.
  12. Avolio C, Filippi M, Tortorella C, Rocca MA, Ruggieri M, Agosta M, Tomassini F, Pozzilli V, Stecchi C, Giaquinto P, Liurea P, Trojano M: Serum MMP−9/TIMP−1 and MMP−2/TIMP−2 ratios in multiple sclerosis: relationship with different magnetic resonance imaging measures of disease activity during IFN−beta−1a treatment. Multiple Sclerosis 2005, 11, 441–446.
  13. Demedts IK, Brusselle GG, Bracke KR, Vermaelen KY, Pauwels RA: Matrix metalloproteinases in asthma and COPD. Curr Opin Pharmacol 2005, 5, 257–263.
  14. Coussens LM, Fingleton B, Matrisian LM: Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science 2002, 295, 2387–2392.
  15. Johnson SR: TIMP−1 in asthma: guilty by association. Thorax 2005, 60, 617–618.
  16. Wenzel SE, Balzar S, Cundall M, Chu HW: Subepithelial basement membrane immunoreactivity for matrix metalloproteinase 9: Association with asthma severity, neutrophilic inflammation, and wound repair. J Allergy Clin Immunol 2003, 111, 1345–1352.
  17. Profita M, Gagliardo R, Di Giorgi R, Bruno A, Riccobono L, Bonanno A, Bousquet J, Vignola AM: In vitro effects of flunisolide on MMP−9, TIMP−1, fibronectin, TGF−β1 release and apoptosis in sputum cells freshly isolated from mild to moderate asthmatics. Allergy 2004, 59, 927–932.
  18. 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, 162, 4212–4219.
  19. Prikk K, Maisi P, Pirila E, Reintam M−A, Salo T, Sorsa T, Sepper R: Airway obstruction correlates with collagenase−2 (MMP−8) expression and activation in bronchial asthma. Lab Invest 2002, 85, 1535–1545.
  20. Cundall M, Sun Y, Miranda C, Trudeau JB, Barnes S, Wenzel SE: Neutrophil−derived matrix metalloproteinase−9 is increased in severe asthma and poorly inhibited by glucocorticoids. J Allergy Clin Immunol 2003, 112, 1064–1071.
  21. Kelly EAB, Busse WW, Jarjour NN: Increased matrix metalloproteinase−9 in the airway after allergen challenge. Am J Respir Crit Care Med 2000, 162, 1157–1161.
  22. Boulay ME, Prince P, Deschesnes F, Chakir J, Boulet LP: Metalloproteinase−9 in induced sputum correlates with the severity of the late allergen−induced asthmatic response. Respiration 2004, 71, 216–224.
  23. Atkinson JJ, Senior RM: Matrix metalloproteinase−9 in lung remodeling. Am J Respir Cell Mol Biol 2003, 28, 12–24.
  24. Elshaw SR, Henderson N, Knox AJ, Watson SA, Buttle DJ, Johnson SR: Matrix metalloproteinase expression and activity in human airway smooth muscle cells. Br J Pharmacol 2004, 142, 1318–1324.
  25. 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, 158, 1945–1950.
  26. Lose F, Thompson PJ, Duffy D, Stewart GA, Kedda M−A: A novel tissue inhibitor of metalloproteinase−1 (TIMP−1) polymorphism associated with asthma in Australian women. Thorax 2005, 60, 623–628.
  27. Baker AH, Edwards DR, Murphy G: Metalloproteinase inhibitors: biological actions and therapeutic opportunities. J Cell Science 2002, 115, 3719–3727.
  28. Mautino G, Henriquet C, Jaffuel D, Bousquet J, Capony F: Tissue inhibitor of metalloproteinase−1 levels in bronchoalveolar lavage fluid from asthmatics subjects. Am J Respir Crit Care Med 1999, 160, 324–330.
  29. Lee KS, Jin SM, Kim HJ, Lee YC: Matrix metalloproteinase inhibitor regulates inflammatory cell migration by reducing ICAM−1 and VCAM−1 expression in a murine model of toluene diisocyanate−induced asthma. J Allergy Clin Immunol 2003, 111, 1278–1284.
  30. Bossé M, Chakir J, Rouabhia M, Boulet L−P, Audette M, Laviolette M: Serum matrix metalloproteinase−9: tissue inhibitor of metalloproteinase−1 ratio correlates with steroid responsiveness in moderate to severe asthma. Am J Respir Crit Care Med 1999, 159, 596–602.
  31. Mattos W, Lim S, Russell R, Jatakanon A, Chung KF, Barnes PJ: Matrix metalloproteinase−9 expression in asthma. Chest 2002, 122, 1543–1552.
  32. Culpitt SV, Rogers DF, Traves SL, Barnes PJ, Donnelly LE: Sputum matrix metalloproteinases: comparison between chronic obstructive pulmonary disease and asthma. Respir Med 2005, 99, 703–710.
  33. Oshita Y, Koga T, Kamimura T, Matsuo K, Rikimaru T, Aizawa H: Increased circulating 92 kDa matrix metalloproteinase (MMP−9) activity in exacerbations of asthma. Thorax 2003, 58, 757–760.
  34. 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, 122, 1553–1559.
  35. Han Z, Junxu, Zhong N: Expression of matrix metalloproteinases MMP−9 within the airways in asthma. Respir Med 2003, 97, 563–567.
  36. Dahlen B, Shute J, Howarth P: Immunohistochemical localization of the matrix metalloproteinases MMP−3 and MMP−9 within the airways in asthma. Thorax 1999, 54, 590–596.
  37. Hoshino M, NakamuraY, Sim J, Shimojo J, Isogai S: Bronchial subepithelial fibrosis and expression of matrix metalloproteinase−9 in asthmatic airway inflammation. J Allergy Clin Immunol 1998, 102, 783–788.
  38. 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, 60, 277–281.
  39. Hoshino M, Takahashi M, Takai Y, Sim J: Inhaled corticosteroids decrease subepithelial collagen deposition by modulation of the balance between matrix metalloproteinase−9 and tissue inhibitor of metalloproteinase−1 expression in asthma. J Allergy Clin Immunol 1999, 104, 356–363.
  40. Slavin J, Unemori E, Hunt TK, Amento E: Transforming growth factor beta (TGF−beta) and dexamethasone have direct opposing effects on collagen metabolism in low passage human dermal fibroblasts in vitro. Growth factors 1994, 11, 205–213.
  41. Shapiro SD, Campbell EJ, Kobayashi DK, Welgus HG: Dexamethasone selectively modulates basal and lipopolysaccharide−induced metalloproteinase and tissue inhibitor of metalloproteinase production by human alveolar macrophages. J Immunol 1991, 146, 2724–2729.
  42. Vanacker NJ, Palmans E, Kips JC, Pauwels RA: Fluticasone inhibits but does not reverse allergen−induced structural airway changes. Am J Respir Crit Care Med 2001, 163, 674–679.
  43. Bruce C, Thomas PS: The effect of marimastat, a metalloprotease inhibitor on allergen−induced asthmatic hyperreactivity. Toxicol Appl Pharmacol 2005, 205, 126–132.
  44. Corry DB, Rishi K, Kanellis J, Kiss A, Song LzLZ, Xu J, Feng L, Werb Z, Kheradmand F: Decreased allergic lung inflammatory cell egression and increased susceptibility to asphyxiation in MMP2−deficiency. Nat Immunol 2002, 3, 347–353.
  45. Martignetti JA, Aqeel AA, Sewairi WA, Boumah CE, Kambouris M, Mayouf SA, Sheth KV, Eid WA, Dowling O, Harris J, Glucksman MJ, Bahabri S, Meyer BF, Desnick RJ: Mutation of the matrix metalloproteinase 2 gene (MMP2) causes a multicentric osteolysis and arthritis syndrome. Nat Genet 2001, 28, 261–265.
© Wroclaw Medical University