Matrix metalloproteinases in airways inflammation of asthma and chronic obstructive pulmonary disease

  • Sum-Yee Leung
  • Kian Fan Chung
Part of the Progress in Inflammation Research book series (PIR)


Matrix metalloproteinases (MMPs) are produced in the respiratory tract from different inflammatory and structural cells and are involved in wound healing, inflammatory cell trafficking and tissue remodelling and repair. MMPs are tightly regulated and their effects are counterbalanced by their physiological inhibitors, tissue inhibitors of MMPs (TIMPs). Increased secretion and expression of MMPs have been reported in asthma and chronic obstructive pulmonary disease (COPD), which are chronic inflammatory lung diseases that lead to chronic airflow obstruction associated with significant mortality and morbidity. Cytokines and growth factors which are involved in these inflammatory processes interact directly with MMPs, leading to a regulation of their expression or changes in their biological activities through enzymatic cleavage. Different MMPs play a specific role with variations in different lung diseases. In COPD, MMP 1, MMP 9 and MMP 12 from lung macrophages play an important role in degradation of matrix leading to emphysema. MMPs may represent relevant therapeutic targets for many diseases. However, their contribution is potentially complex since MMPs may have both beneficial as well as deleterious effects. Thus, some actions may lead to pro-inflammatory effects, while others may also cause anti-inflammatory effects. Therefore, the precise role of these MMPs in airways disease with airflow obstruction need to be clarified carefully before selective MMP inhibitors are tried for therapeutic aims in these diseases.


Chronic Obstructive Pulmonary Disease Chronic Obstructive Pulmonary Disease Patient Airway Inflammation Airway Smooth Muscle Respir Crit 
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.


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  1. 1.
    Gross J, Lapiere CM (1962) Collagenolytic activity in amphibian tissues: a tissue culture assay. Proc Natl Acad Sci USA 48: 1014–1022PubMedCrossRefGoogle Scholar
  2. 2.
    Brinckerhoff CE, Matrisian LM (2002) Matrix metalloproteinases: a tail of a frog that became a prince. Nat Rev Mol Cell Biol 3: 207–214PubMedCrossRefGoogle Scholar
  3. 3.
    Davidson JM (1990) Biochemistry and turnover of lung interstitium. Eur Respir J 3: 1048–1063PubMedGoogle Scholar
  4. 4.
    Van Wart HE, Birkedal-Hansen H (1990) The cysteine switch: a principle of regulation of metalloproteinase activity with potential applicability to the entire matrix metalloproteinase gene family. Proc Natl Acad Sci USA 87: 5578–5582PubMedCrossRefGoogle Scholar
  5. 5.
    Brew K, Dinakarpandian D, Nagase H (2000) Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochim Biophys Acta 1477: 267–283PubMedGoogle Scholar
  6. 6.
    Bousquet J, Jeffery PK, Busse WW, Johnson M, Vignola AM (2000) Asthma. From bronchoconstriction to airways inflammation and remodeling. Am J Respir Crit Care Med 161: 1720–1745PubMedGoogle Scholar
  7. 7.
    Hogg JC (2004) Pathophysiology of airflow limitation in chronic obstructive pulmonary disease. Lancet 364: 709–721PubMedCrossRefGoogle Scholar
  8. 8.
    Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, Buzatu L, Cherniack RM, Rogers RM, Sciurba FC, Coxson HO et al. (2004) The nature of small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med 350: 2645–2653PubMedCrossRefGoogle Scholar
  9. 9.
    Kim WD, Eidelman DH, Izquierdo JL, Ghezzo H, Saetta MP, Cosio MG (1991) Centrilobular and panlobular emphysema in smokers. Two distinct morphologic and functional entities. Am Rev Respir Dis 144: 1385–1390PubMedGoogle Scholar
  10. 10.
    Barnes PJ, Shapiro SD, Pauwels RA (2003) Chronic obstructive pulmonary disease: molecular and cellular mechanisms. Eur Respir J 22: 672–688PubMedCrossRefGoogle Scholar
  11. 11.
    Parks WC, Shapiro SD (2001) Matrix metalloproteinases in lung biology. Respir Res 2: 10–19PubMedCrossRefGoogle Scholar
  12. 12.
    Yao PM, Buhler JM, d’Ortho MP, Lebargy F, Delclaux C, Harf A, Lafuma C (1996) Expression of matrix metalloproteinase gelatinases A and B by cultured epithelial cells from human bronchial explants. J Biol Chem 271: 15580–15589PubMedCrossRefGoogle Scholar
  13. 13.
    Dunsmore SE, Saarialho-Kere UK, Roby JD, Wilson CL, Matrisian LM, Welgus HG, Parks WC (1998) Matrilysin expression and function in airway epithelium. J Clin Invest 102: 1321–1331PubMedCrossRefGoogle Scholar
  14. 14.
    Mercer BA, Kolesnikova N, Sonett J, D’Armiento J (2004) Extracellular regulated kinase/mitogen activated protein kinase is up-regulated in pulmonary emphysema and mediates matrix metalloproteinase-1 induction by cigarette smoke. J Biol Chem 279: 17690–17696PubMedCrossRefGoogle Scholar
  15. 15.
    Xu J, Benyon RC, Leir SH, Zhang S, Holgate ST, Lackie PM (2002) Matrix metalloproteinase-2 from bronchial epithelial cells induces the proliferation of subepithelial fibroblasts. Clin Exp Allergy 32: 881–888PubMedCrossRefGoogle Scholar
  16. 16.
    Lavigne MC, Thakker P, Gunn J, Wong A, Miyashiro JS, Wasserman AM, Wei SQ, Pelker JW, Kobayashi M, Eppihimer MJ (2004) Human bronchial epithelial cells express and secrete MMP-12. Biochem Biophys Res Commun 324: 534–546PubMedCrossRefGoogle Scholar
  17. 17.
    Campbell EJ, Cury JD, Shapiro SD, Goldberg GI, Welgus HG (1991) Neutral proteinases of human mononuclear phagocytes. Cellular differentiation markedly alters cell phenotype for serine proteinases, metalloproteinases, and tissue inhibitor of metalloproteinases. J Immunol 146: 1286–1293PubMedGoogle Scholar
  18. 18.
    Cataldo DD, Bettiol J, Noel A, Bartsch P, Foidart JM, Louis R (2002) Matrix metalloproteinase-9, but not tissue inhibitor of matrix metalloproteinase-1, increases in the sputum from allergic asthmatic patients after allergen challenge. Chest 122: 1553–1559PubMedCrossRefGoogle Scholar
  19. 19.
    Takafuji S, Ishida A, Miyakuni Y, Nakagawa T (2003) Matrix metalloproteinase-9 release from human leukocytes. J Investig Allergol Clin Immunol 13: 50–55PubMedGoogle Scholar
  20. 20.
    Claesson R, Johansson A, Belibasakis G, Hanstrom L, Kalfas S (2002) Release and activation of matrix metalloproteinase 8 from human neutrophils triggered by the leukotoxin of Actinobacillus actinomycetemcomitans. J Periodontal Res 37: 353–359PubMedCrossRefGoogle Scholar
  21. 21.
    Elshaw SR, Henderson N, Knox AJ, Watson SA, Buttle DJ, Johnson SR (2004) Matrix metalloproteinase expression and activity in human airway smooth muscle cells. Br J Pharmacol 142: 1318–1324PubMedCrossRefGoogle Scholar
  22. 22.
    Rajah R, Nunn SE, Herrick DJ, Grunstein MM, Cohen P (1996) Leukotriene D4 induces MMP-1, which functions as an IGFBP protease in human airway smooth muscle cells. Am J Physiol 271: L1014–L1022PubMedGoogle Scholar
  23. 23.
    Foda HD, George S, Rollo E, Drews M, Conner C, Cao J, Panettieri Jr RA, Zucker S (1999) Regulation of gelatinases in human airway smooth muscle cells: mechanism of progelatinase A activation. Am J Physiol 277: L174–L182PubMedGoogle Scholar
  24. 24.
    Johnson S, Knox A (1999) Autocrine production of matrix metalloproteinase-2 is required for human airway smooth muscle proliferation. Am J Physiol 277: L1109–L1117PubMedGoogle Scholar
  25. 25.
    Dahlen B, Shute J, Howarth P (1999) Immunohistochemical localisation of the matrix metalloproteinases MMP-3 and MMP-9 within the airways in asthma. Thorax 54: 590–596PubMedCrossRefGoogle Scholar
  26. 26.
    Liang KC, Lee CW, Lin WN, Lin CC, Wu CB, Luo SF, Yang CM (2007) Interleukin-1beta induces MMP-9 expression via p42/p44 MAPK, p38 MAPK, JNK, and nuclear factor-kappaB signaling pathways in human tracheal smooth muscle cells. J Cell Physiol 211: 759–770PubMedCrossRefGoogle Scholar
  27. 27.
    Xie S, Sukkar MB, Issa R, Oltmanns U, Nicholson AG, Chung KF (2005) Regulation of TGF-β1-induced connective tissue growth factor expression in airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 2288: L68–L76PubMedCrossRefGoogle Scholar
  28. 28.
    Xie S, Issa R, Sukkar MB, Oltmanns U, Bhavsar PK, Papi A, Caramori G, Adcock I, Chung KF (2005) Induction and regulation of matrix metalloproteinase-12 in human airway smooth muscle cells. Respir Res 6: 148PubMedCrossRefGoogle Scholar
  29. 29.
    Chandler S, Cossins J, Lury J, Wells G (1996) Macrophage metalloelastase degrades matrix and myelin proteins and processes a tumour necrosis factor-alpha fusion protein. Biochem Biophys Res Commun 228: 421–429PubMedCrossRefGoogle Scholar
  30. 30.
    Imai K, Hiramatsu A, Fukushima D, Pierschbacher MD, Okada Y (1997) Degradation of decorin by matrix metalloproteinases: identification of the cleavage sites, kinetic analyses and transforming growth factor-beta1 release. Biochem J 322 (Pt 3): 809–814PubMedGoogle Scholar
  31. 31.
    Fowlkes JL, Enghild JJ, Suzuki K, Nagase H (1994) Matrix metalloproteinases degrade insulin-like growth factor-binding protein-3 in dermal fibroblast cultures. J Biol Chem 269: 25742–25746PubMedGoogle Scholar
  32. 32.
    Noveral JP, Bhala A, Hintz RL, Grunstein MM, Cohen P (1994) Insulin-like growth factor axis in airway smooth muscle cells. Am J Physiol 267: L761–L765PubMedGoogle Scholar
  33. 33.
    Hasaneen NA, Zucker S, Cao J, Chiarelli C, Panettieri RA, Foda HD (2005) Cyclic mechanical strain-induced proliferation and migration of human airway smooth muscle cells: role of EMMPRIN and MMPs. FASEB J 19:1507–1509PubMedGoogle Scholar
  34. 34.
    Lanone S, Zheng T, Zhu Z, Liu W, Lee CG, Ma B, Chen Q, Homer RJ, Wang J, Rabach LA et al (2002) Overlapping and enzyme-specific contributions of matrix metalloproteinases-9 and-12 in IL-13-induced inflammation and remodeling. J Clin Invest 110: 463–474PubMedGoogle Scholar
  35. 35.
    Hautamaki RD, Kobayashi DK, Senior RM, Shapiro SD (1997) Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice. Science 277: 2002–2004PubMedCrossRefGoogle Scholar
  36. 36.
    Mautino G, Oliver N, Chanez P, Bousquet J, Capony F (1997) Increased release of matrix metalloproteinase-9 in bronchoalveolar lavage fluid and by alveolar macrophages of asthmatics. Am J Respir Cell Mol Biol 17: 583–591PubMedGoogle Scholar
  37. 37.
    Cataldo D, Munaut C, Noel A, Frankenne F, Bartsch P, Foidart JM, Louis R (2000) MMP-2-and MMP-9-linked gelatinolytic activity in the sputum from patients with asthma and chronic obstructive pulmonary disease. Int Arch Allergy Immunol 123: 259–267PubMedCrossRefGoogle Scholar
  38. 38.
    Vignola AM, Riccobono L, Mirabella A, Profita M, Chanez P, Bellia V, Mautino G, D’accardi P, Bousquet J, Bonsignore G (1998) Sputum metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio correlates with airflow obstruction in asthma and chronic bronchitis. Am J Respir Crit Care Med 158: 1945–1950PubMedGoogle Scholar
  39. 39.
    Bosse M, Chakir J, Rouabhia M, Boulet LP, Audette M, Laviolette M (1999) 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 159: 596–602PubMedGoogle Scholar
  40. 40.
    Cataldo DD, Gueders M, Munaut C, Rocks N, Bartsch P, Foidart JM, Noel A, Louis R (2004) Matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases mRNA transcripts in the bronchial secretions of asthmatics. Lab Invest 84: 418–424PubMedCrossRefGoogle Scholar
  41. 41.
    Cataldo D, Munaut C, Noel A, Frankenne F, Bartsch P, Foidart JM, Louis R (2001) Matrix metalloproteinases and TIMP-1 production by peripheral blood granulocytes from COPD patients and asthmatics. Allergy 56: 145–151PubMedCrossRefGoogle Scholar
  42. 42.
    Prause O, Bozinovski S, Anderson GP, Linden A (2004) Increased matrix metalloproteinase-9 concentration and activity after stimulation with interleukin-17 in mouse airways. Thorax 59: 313–317PubMedCrossRefGoogle Scholar
  43. 43.
    Ohno I, Ohtani H, Nitta Y, Suzuki J, Hoshi H, Honma M, Isoyama S, Tanno Y, Tamura G, Yamauchi K et al (1997) Eosinophils as a source of matrix metalloproteinase-9 in asthmatic airway inflammation. Amer J Respir Cell Mol Biol 16: 212–219Google Scholar
  44. 44.
    Han Z, Junxu, Zhong N (2003) Expression of matrix metalloproteinases MMP-9 within the airways in asthma. Respir Med 97: 563–567PubMedCrossRefGoogle Scholar
  45. 45.
    Mattos W, Lim S, Russell R, Jatakanon A, Chung KF, Barnes PJ (2002) Matrix metalloproteinase-9 expression in asthma: effect of asthma severity, allergen challenge, and inhaled corticosteroids. Chest 122: 1543–1552PubMedCrossRefGoogle Scholar
  46. 46.
    Belleguic C, Corbel M, Germain N, Lena H, Boichot E, Delaval PH, Lagente V (2002) Increased release of matrix metalloproteinase-9 in the plairway smooth musclea of acute severe asthmatic patients. Clin Exp Allergy 32: 217–223PubMedCrossRefGoogle Scholar
  47. 47.
    Wenzel SE, Balzar S, Cundall M, Chu HW (2003) Subepithelial basement membrane immunoreactivity for matrix metalloproteinase 9: association with asthma severity, neutrophilic inflammation, and wound repair. J Allergy Clin Immunol 111: 1345–1352PubMedCrossRefGoogle Scholar
  48. 48.
    Cundall M, Sun Y, Miranda C, Trudeau JB, Barnes S, Wenzel SE (2003) Neutrophilderived matrix metalloproteinase-9 is increased in severe asthma and poorly inhibited by glucocorticoids. J Allergy Clin Immunol 112: 1064–1071PubMedCrossRefGoogle Scholar
  49. 49.
    Lee YC, Lee HB, Rhee YK, Song CH (2001) The involvement of matrix metalloproteinase-9 in airway inflammation of patients with acute asthma. Clin Exp Allergy 31: 1623–1630PubMedCrossRefGoogle Scholar
  50. 50.
    Oshita Y, Koga T, Kamimura T, Matsuo K, Rikimaru T, Aizawa H (2003) Increased circulating 92 kDa matrix metalloproteinase (MMP-9) activity in exacerbations of asthma. Thorax 58: 757–760PubMedCrossRefGoogle Scholar
  51. 51.
    Pham DN, Chu HW, Martin RJ, Kraft M (2003) Increased matrix metalloproteinase-9 with elastolysis in nocturnal asthma. Ann Allergy Asthma Immunol 90: 72–78PubMedCrossRefGoogle Scholar
  52. 52.
    Boulay ME, Prince P, Deschesnes F, Chakir J, Boulet LP (2004) Metalloproteinase-9 in induced sputum correlates with the severity of the late allergen-induced asthmatic response. Resp 71: 216–224Google Scholar
  53. 53.
    Kelly EA, Busse WW, Jarjour NN (2000) Increased matrix metalloproteinase-9 in the airway after allergen challenge. Am J Respir Crit Care Med 162: 1157–1161PubMedGoogle Scholar
  54. 54.
    Beeh KM, Beier J, Kornmann O, Buhl R (2003) Sputum matrix metalloproteinase-9, tissue inhibitor of metalloprotinease-1, and their molar ratio in patients with chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and healthy subjects. Respir Med 97: 634–639PubMedCrossRefGoogle Scholar
  55. 55.
    Finlay GA, O’Driscoll LR, Russell KJ, D’Arcy EM, Masterson JB, FitzGerald MX, O’Connor CM (1997) Matrix metalloproteinase expression and production by alveolar macrophages in emphysema. Am J Respir Crit Care Med 156: 240–247PubMedGoogle Scholar
  56. 56.
    Betsuyaku T, Nishimura M, Takeyabu K, Tanino M, Venge P, Xu S, Kawakami Y (1999) Neutrophil granule proteins in bronchoalveolar lavage fluid from subjects with subclinical emphysema. Am J Respir Crit Care Med 159: 1985–1991PubMedGoogle Scholar
  57. 57.
    Lim S, Roche N, Oliver BG, Mattos W, Barnes PJ, Chung KF (2000) Balance of matrix metalloprotease-9 and tissue inhibitor of metalloprotease-1 from alveolar macrophages in cigarette smokers. Regulation by interleukin-10. Am J Respir Crit Care Med 162: 1355–1360PubMedGoogle Scholar
  58. 58.
    Russell RE, Culpitt SV, DeMatos C, Donnelly L, Smith M, Wiggins J, Barnes PJ (2002) Release and activity of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 by alveolar macrophages from patients with chronic obstructive pulmonary disease. Amer J Respir Cell Mol Biol 26: 602–609Google Scholar
  59. 59.
    Segura-Valdez L, Pardo A, Gaxiola M, Uhal BD, Becerril C, Selman M (2000) Upregulation of gelatinases A and B, collagenases 1 and 2, and increased parenchymal cell death in COPD. Chest 117: 684–694PubMedCrossRefGoogle Scholar
  60. 60.
    Imai K, Dalal SS, Chen ES, Downey R, Schulman LL, Ginsburg M, D’Armiento J (2001) Human collagenase (matrix metalloproteinase-1) expression in the lungs of patients with emphysema. Am J Respir Crit Care Med 163: 786–791PubMedGoogle Scholar
  61. 61.
    Kang MJ, Oh YM, Lee JC, Kim DG, Park MJ, Lee MG, Hyun IG, Han SK, Shim YS, Jung KS (2003) Lung matrix metalloproteinase-9 correlates with cigarette smoking and obstruction of airflow. J Korean Med Sci 18: 821–827PubMedGoogle Scholar
  62. 62.
    Minematsu N, Nakamura H, Tateno H, Nakajima T, Yamaguchi K (2001) Genetic polymorphism in matrix metalloproteinase-9 and pulmonary emphysema. Biochem Biophys Res Commun 289: 116–119PubMedCrossRefGoogle Scholar
  63. 63.
    D’Armiento J, Dalal SS, Okada Y, Berg RA, Chada K (1992) Collagenase expression in the lungs of transgenic mice causes pulmonary emphysema. Cell 71: 955–961PubMedCrossRefGoogle Scholar
  64. 64.
    Molet S, Belleguic C, Lena H, Germain N, Bertrand CP, Shapiro SD, Planquois JM, Delaval P, Lagente V (2005) Increase in macrophage elastase (MMP-12) in lungs from patients with chronic obstructive pulmonary disease. Inflamm Res 54: 31–36PubMedCrossRefGoogle Scholar
  65. 65.
    Demedts IK, Morel-Montero A, Lebecque S, Pacheco Y, Cataldo D, Joos GF, Pauwels RA, Brusselle GG (2006) Elevated MMP-12 protein levels in induced sputum from patients with COPD. Thorax 61: 196–201PubMedCrossRefGoogle Scholar
  66. 66.
    Montano M, Beccerril C, Ruiz V, Ramos C, Sansores RH, Gonzalez-Avila G (2004) Matrix metalloproteinases activity in COPD associated with wood smoke. Chest 125: 466–472PubMedCrossRefGoogle Scholar
  67. 67.
    Joos L, He JQ, Shepherdson MB, Connett JE, Anthonisen NR, Pare PD, Sandford AJ (2002) The role of matrix metalloproteinase polymorphisms in the rate of decline in lung function. Hum Mol Genet 11: 569–576PubMedCrossRefGoogle Scholar
  68. 68.
    Shapiro SD (2002) Proteinases in chronic obstructive pulmonary disease. Biochem Soc Trans 30: 98–102PubMedCrossRefGoogle Scholar
  69. 69.
    Lappalainen U, Whitsett JA, Wert SE, Tichelaar JW, Bry K (2005) Interleukin-1beta causes pulmonary inflammation, emphysema, and airway remodeling in the adult murine lung. Am J Respir Cell Mol Biol 32: 311–318PubMedCrossRefGoogle Scholar
  70. 70.
    Churg A, Wang R, Wang X, Onnervik PO, Thim K, Wright JL (2007) Effect of an MMP-9/MMP-12 inhibitor on smoke-induced emphysema and airway remodelling in guinea pigs. Thorax 62: 706–713PubMedCrossRefGoogle Scholar
  71. 71.
    Shapiro SD, Kobayashi DK, Ley TJ (1993) Cloning and characterization of a unique elastolytic metalloproteinase produced by human alveolar macrophages. J Biol Chem 268: 23824–23829PubMedGoogle Scholar
  72. 72.
    Chandler S, Cossins J, Lury J, Wells G (1996) Macrophage metalloelastase degrades matrix and myelin proteins and processes a tumour necrosis factor-alpha fusion protein. Biochem Biophys Res Commun 228: 421–429PubMedCrossRefGoogle Scholar
  73. 73.
    Gronski TJ Jr, Martin RL, Kobayashi DK, Walsh BC, Holman MC, Huber M, Van Wart HE, Shapiro SD (1997) Hydrolysis of a broad spectrum of extracellular matrix proteins by human macrophage elastase. J Biol Chem 272: 12189–12194PubMedCrossRefGoogle Scholar
  74. 74.
    Matsumoto S, Kobayashi T, Katoh M, Saito S, Ikeda Y, Kobori M, Masuho Y, Watanabe T (1998) Expression and localization of matrix metalloproteinase-12 in the aorta of cholesterol-fed rabbits: relationship to lesion development. Am J Pathol 153: 109–119PubMedGoogle Scholar
  75. 75.
    Bracke K, Cataldo D, Maes T, Gueders M, Noel A, Foidart JM, Brusselle G, Pauwels RA (2005) Matrix metalloproteinase-12 and cathepsin D expression in pulmonary macrophages and dendritic cells of cigarette smoke-exposed mice. Int Arch Allergy Immunol 138: 169–179PubMedCrossRefGoogle Scholar
  76. 76.
    Churg A, Wang RD, Tai H, Wang X, Xie C, Dai J, Shapiro SD, Wright JL (2003) Macrophage metalloelastase mediates acute cigarette smoke-induced inflammation via tumor necrosis factor-alpha release. Am J Respir Crit Care Med 167: 1083–1089PubMedCrossRefGoogle Scholar
  77. 77.
    Pouladi MA, Robbins CS, Swirski FK, Cundall M, McKenzie AN, Jordana M, Shapiro SD, Stampfli M (2004) Interleukin-13-dependent expression of matrix metalloproteinase-12 is required for the development of airway eosinophilia in mice. Am J Respir Cell Mol Biol 30: 84–90PubMedCrossRefGoogle Scholar
  78. 78.
    Lanone S, Zheng T, Zhu Z, Liu W, Lee CG, Ma B, Chen Q, Homer RJ, Wang J, Rabach LA et al (2002) Overlapping and enzyme-specific contributions of matrix metalloproteinases-9 and-12 in IL-13-induced inflammation and remodeling. J Clin Invest 110: 463–474PubMedGoogle Scholar
  79. 79.
    Zheng T, Zhu Z, Wang Z, Homer RJ, Ma B, Riese RJ, Chapman HA, Shapiro SD, Elias JA (2000) Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase-and cathepsin-dependent emphysema. J Clin Invest 106: 1081–1093PubMedCrossRefGoogle Scholar
  80. 80.
    Lee CG, Homer RJ, Zhu Z, Lanone S, Wang X, Koteliansky V, Shipley JM, Gotwals P, Noble P, Chen Q et al (2001) Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor beta(1). J Exp Med 194: 809–821PubMedCrossRefGoogle Scholar
  81. 81.
    Maeda S, Dean DD, Gomez R, Schwartz Z, Boyan BD (2002) The first stage of transforming growth factor beta1 activation is release of the large latent complex from the extracellular matrix of growth plate chondrocytes by matrix vesicle stromelysin-1 (MMP-3). Calcif Tissue Int 70: 54–65PubMedCrossRefGoogle Scholar
  82. 82.
    Yu Q, Stamenkovic I (2000) Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Genes Dev 14: 163–176PubMedGoogle Scholar
  83. 83.
    Karsdal MA, Larsen L, Engsig MT, Lou H, Ferreras M, Lochter A, Delaisse JM, Foged NT (2002) Matrix metalloproteinase-dependent activation of latent transforming growth factor-beta controls the conversion of osteoblasts into osteocytes by blocking osteoblast apoptosis. J Biol Chem 277: 44061–44067PubMedCrossRefGoogle Scholar
  84. 84.
    McQuibban GA, Gong JH, Wong JP, Wallace JL, Clark-Lewis I, Overall CM (2002) Matrix metalloproteinase processing of monocyte chemoattractant proteins generates CC chemokine receptor antagonists with anti-inflammatory properties in vivo. Blood 100: 1160–1167PubMedGoogle Scholar
  85. 85.
    Van den Steen PE, Proost P, Wuyts A, Van Damme J, Opdenakker G (2000) Neutrophil gelatinase B potentiates interleukin-8 tenfold by aminoterminal processing, whereas it degrades CTAP-III, PF-4, and GRO-alpha and leaves RANTES and MCP-2 intact. Blood 96: 2673–2681PubMedGoogle Scholar
  86. 86.
    Van den Steen PE, Wuyts A, Husson SJ, Proost P, Van Damme J, Opdenakker G (2003) Gelatinase B/MMP-9 and neutrophil collagenase/MMP-8 process the chemokines human GCP-2/CXCL6, ENA-78/CXCL5 and mouse GCP-2/LIX and modulate their physiological activities. Eur J Biochem 270: 3739–3749CrossRefGoogle Scholar
  87. 87.
    Corry DB, Kiss A, Song LZ, Song L, Xu J, Lee SH, Werb Z, Kheradmand F (2004) Overlapping and independent contributions of MMP2 and MMP9 to lung allergic inflammatory cell egression through decreased CC chemokines. FASEB J 18: 995–997PubMedGoogle Scholar
  88. 88.
    Corry DB, Rishi K, Kanellis J, Kiss A, Song LZ, Xu J, Feng L, Werb Z, Kheradmand F (2002) Decreased allergic lung inflammatory cell egression and increased susceptibility to asphyxiation in MMP2-deficiency. Nat Immunol 3: 347–353PubMedCrossRefGoogle Scholar
  89. 89.
    Houghton AM, Quintero PA, Perkins DL, Kobayashi DK, Kelley DG, Marconcini LA, Mecham RP, Senior RM, Shapiro SD (2006) Elastin fragments drive disease progression in a murine model of emphysema. J Clin Invest 116: 753–759PubMedCrossRefGoogle Scholar
  90. 90.
    Bergers G, Brekken R, McMahon G, Vu TH, Itoh T, Tamaki K, Tanzawa K, Thorpe P, Itohara S, Werb Z et al. (2000) Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol 2: 737–744PubMedCrossRefGoogle Scholar
  91. 91.
    Suzuki M, Raab G, Moses MA, Fernandez CA, Klagsbrun M (1997) Matrix metalloproteinase-3 releases active heparin-binding EGF-like growth factor by cleavage at a specific juxtamembrane site. J Biol Chem 272: 31730–31737PubMedCrossRefGoogle Scholar
  92. 92.
    Lee KS, Min KH, Kim SR, Park SJ, Park HS, Jin GY, Lee YC (2006) Vascular endothelial growth factor modulates matrix metalloproteinase-9 expression in asthma. Am J Respir Crit Care Med 174: 161–170PubMedCrossRefGoogle Scholar
  93. 93.
    Santibanez JF, Guerrero J, Quintanilla M, Fabra A, Martinez J (2002) Transforming growth factor-beta1 modulates matrix metalloproteinase-9 production through the Ras/MAPK signaling pathway in transformed keratinocytes. Biochem Biophys Res Commun 296: 267–273PubMedCrossRefGoogle Scholar
  94. 94.
    Rajah R, Nachajon RV, Collins MH, Hakonarson H, Grunstein MM, Cohen P (1999) Elevated levels of the IGF-binding protein protease MMP-1 in asthmatic airway smooth muscle. Amer J Respir Cell Mol Biol 20: 199–208Google Scholar
  95. 95.
    Zhang D, Bar-Eli M, Meloche S, Brodt P (2004) Dual regulation of MMP-2 expression by the type 1 insulin-like growth factor receptor: the phosphatidylinositol 3-kinase/Akt and Raf/ERK pathways transmit opposing signals. J Biol Chem 279: 19683–19690PubMedCrossRefGoogle Scholar

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© Birkhäuser Verlag Basel/Switzerland 2008

Authors and Affiliations

  • Sum-Yee Leung
    • 1
  • Kian Fan Chung
    • 1
  1. 1.Experimental Medicine/Airway Disease Section, National Heart & Lung InstituteImperial College LondonLondonUK

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