Protease inhibitors in respiratory disease: Focus on asthma and chronic obstructive pulmonary disease

Expert Review of Clinical Immunology

Volumn 3, Issue 3, 2007, Pages 365-381

  Venkatasamy, Radhakishnan ^a   Spina, Domenico ^a  

^a KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

Asthma; Chronic obstructive pulmonary disease; COPD; Elastase; Inflammation; Matrix metalloprotease; Remodelling; Tryptase

Indexed keywords

AMG 126737; BETA TRYPTASE INHIBITOR; COMPOUND 13; CP 471; CP 471474; CP 474; FR 134043; FR 901277; GABEXATE MESILATE; GELATINASE B; GLUCOCORTICOID; ILOMASTAT; LEUKOCYTE ELASTASE; LEUKOCYTE ELASTASE INHIBITOR; MATRIX METALLOPROTEINASE INHIBITOR; MIDESTEINE; MOL 6131; N (1 HYDROXY 2 NAPHTHOYL)ARGINYLPROLINAMIDE; NAFAMSTAT MESILATE; NEUTROPHIL COLLAGENASE; ONO 6818; PHOSPHODIESTERASE IV INHIBITOR; PROTEINASE ACTIVATED RECEPTOR BLOCKING AGENT; PROTEINASE INHIBITOR; RECEPTOR BLOCKING AGENT; RS 113456; RWJ 58643; TRYPTASE INHIBITOR; UNCLASSIFIED DRUG; UNINDEXED DRUG; ZD 0892;

AIRWAY CONDUCTANCE; ALLERGY; ANTIINFLAMMATORY ACTIVITY; ARTHRALGIA; ARTHRITIS; ASTHMA; CHRONIC OBSTRUCTIVE LUNG DISEASE; CIGARETTE SMOKING; CLINICAL TRIAL; CORTICOSTEROID INDUCED OSTEOPOROSIS; DISEASE PREDISPOSITION; DRUG EFFICACY; DRUG SYNTHESIS; DRUG TARGETING; ENZYME ACTIVITY; EOSINOPHILIA; HUMAN; IC 50; LUNG COMPLIANCE; LUNG EMPHYSEMA; LUNG FUNCTION; MAST CELL; MUSCLE STIFFNESS; NEUTROPHIL CHEMOTAXIS; NONHUMAN; PROTEIN EXPRESSION; REVIEW; RISK FACTOR; TENDINITIS;

EID: 34249775803     PISSN: 1744666X     EISSN: None     Source Type: Journal    
DOI: 10.1586/1744666X.3.3.365     Document Type: Review

References (157)

1. Bergeron C, Boulet LP. Structural changes in airway diseases: characteristics, mechanisms, consequences, and pharmacologic modulation. Chest 129, 1068-1087 (2006).
2. Masoli M, Fabian D, Holt S, Beasley R. The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy 59, 469-478 (2004).
3. Weiss KB, Gergen PJ, Hodgson TA. An economic evaluation of asthma in the United States. N. Engl. J. Med. 326, 862-866 (1992).
4. Hogg JC, Chu F, Utokaparch S et al. The nature of small-airway obstruction in chronic obstructive pulmonary disease. N. Engl. J. Med. 350, 2645-2653 (2004)
5. Stang P, Lydick E, Silberman C, Kempel A, Keating ET. The prevalence of COPD: using smoking rates to estimate disease frequency in the general population. Chest 117, S354-S359 (2000).
6. Pauwels RA, Buist AS, Calverley PM, Jenkins CR, Hurd SS. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) workshop summary. Am. J. Respir. Crit. Care Med. 163, 1256-1276 (2005).
7. Bachelet I, Munitz A, Levi-Schaffer F. Tryptase as an inflammatory marker in allergic disease and asthma. Expert Rev. Clin. Immunol. 1(1), 63-75 (2005).
8. Hallgren J, Pejler G. Biology of mast cell tryptase. An inflammatory mediator. FEBS J. 273, 1871-1895 (2006).
9. Brightling CE, Bradding P, Symon FA, Holgate ST, Wardlaw AJ, Pavord ID. Mast-cell infiltration of airway smooth muscle in asthma. N. Engl. J. Med. 346, 1699-1705 (2002).
10. Amin K, Janson C, Boman G, Venge P. The extracellular deposition of mast cell products is increased in hypertrophic airways smooth muscles in allergic asthma but not in nonallergic asthma. Allergy 60, 1241-1247 (2005).
11. Tam EK, Caughey GH. Degradation of airway neuropeptides by human lung tryptase. Am. J. Respir. Cell. Mol. Biol. 3, 27-32 (1990).
12. Bradding P. Walls AF, Holgate ST. The role of the mast cell in the pathophysiology of asthma. J. Allergy Clin. Immunol. 117, 1277-1284 (2006).
13. Berger P, Perng DW, Thabrew H et al. Tryptase and agonists of PAR-2 induce the proliferation of human airway smooth muscle cells. J. Appl. Physiol. 91, 1372-1379 (2001).
14. Beckett PA, Howarth PH. Pharmacotherapy and airway remodelling in asthma? Thorax 58, 163-174 (2003).
15. Chung KF, Adcock IM. Combination therapy of long-acting β2-adrenoceptor agonists and corticosteroids for asthma. Treat. Respir. Med. 3, 279-289 (2004).
16. Ward C, Walters H. Airway wall remodelling: the influence of corticosteroids. Curr. Opin. Allergy Clin. Immunol. 5, 43-48 (2005).
17. Boxall C, Holgate ST, Davies DE. The contribution of transforming growth factor-β and epidermal growth factor signalling to airway remodelling in chronic asthma. Eur Respir. J. 27, 208-229 (2006).
18. Horvath G, Wanner A. Inhaled corticosteroids: effects on the airway vasculature in bronchial asthma. Eur Respir. J. 27, 172-187 (2006).
19. Takeda K, Hamelmann E, Joetham A et al. Development of eosinophilic airway inflammation and airway hyperresponsiveness in mast cell-deficient mice. J. Exp. Med. 186, 449-454 (1997).
20. Korsgren M, Erjefalt JS, Korsgren O, Sundler F, Persson CG. Allergic eosinophil-rich inflammation develops in lungs and airways of B cell-deficient mice. J. Exp. Med. 185, 885-892 (1997).
21. Hamelmann E, Vella AT, Oshiba A, Kappler JW, Marrack P, Gelfand EW. Allergic airway sensitization induces T cell activation but not airway hyperresponsiveness in B cell-deficient mice. Proc. Natl. Acad. Sci. USA 94, 1350-1355 (1997).
22. MacLean JA, Sauty A, Luster AD, Drazen JM, De Sanctis GT. Antigen-induced airway hyperresponsiveness, pulmonary eosinophilia, and chemokine expression in B cell-deficient mice. Am. J. Respir. Cell. Mol. Biol. 20, 379-387 (1999).
23. Mehlhop PD, van de RM, Goldberg AB et al.. Allergen-induced bronchial hyperreactivity and eosinophilic inflammation occur in the absence of IgE in a mouse model of asthma. Proc. Natl. Acad. Sci. USA 94, 1344-1349 (1997).
24. Riffo-Vasquez Y, Spina D, Thomas M, Gilbey T, Kemeny DM, Page CP. The role of CD23 on allergen-induced IgE levels, pulmonary eosinophilia and bronchial hyperresponsiveness in mice. Clin. Exp. Allergy 30, 728-738 (2000).
25. Hunt JE, Stevens RL, Austen KF, Zhang J, Xia Z, Ghildyal N. Natural disruption of the mouse mast cell protease 7 gene in the C57BL/6 mouse. J. Biol. Chem. 271, 2851-2855 (1996).
26. Rauter I, Krauth MT, Flicker S et al. Allergen cleavage by effector cell-derived proteases regulates allergic inflammation. FASEB J. 20, 967-969 (2006).
27. Cairns JA. Inhibitors of mast cell tryptase beta as therapeutics for the treatment of asthma and inflammatory disorders. Pulm. Pharmacol Ther. 18, 55-66 (2005).
28. Krishna MT, Chauhan A, Little L et al. Inhibition of mast cell tryptase by inhaled APC 366 attenuates allergen-induced late-phase air-way obstruction in asthma. J. Allergy Clin. Immunol. 107, 1039-1045 (2001).
29. Yu M, Tsai M, Tam SY, Jones C, Zehnder J, Galli SJ. Mast cells can promote the development of multiple features of chronic asthma in mice. J. Clin. Invest. 116, 1633-1641 (2006).
30. Reed CE, Kita H. The role of protease activation of inflammation in allergic respiratory diseases. J. Allergy Clin. Immunol. 114, 997-1008 (2004).
31. Knight DA, Lim S, Scaffidi AK et al. Protease-activated receptors in human airways: upregulation of PAR-2 in respiratory epithelium from patients with asthma. J. Allergy Clin. Immunol. 108, 797-803 (2001).
32. Vliagoftis H, Schwingshackl A, Milne CD et al. Proteinase-activated receptor-2-mediated matrix metalloproteinase-9 release from airway epithelial cells. J. Allergy Clin. Immunol. 106, 537-545 (2000).
33. Schmidlin F, Amadesi S, Dabbagh K et al. Protease-activated receptor 2 mediates eosinophil infiltration and hyperreactivity in allergic inflammation of the airway. J. Immunol. 169, 5315-5321 (2002).
34. Ebeling C, Forsythe P, Ng J, Gordon JR, Hollenberg M, Vliagoftis H. Proteinase-activated receptor 2 activation in the airways enhances antigen-mediated airway inflammation and airway hyperresponsiveness through different pathways. J. Allergy Clin. Immunol. 115, 623-630 (2005).
35. De Campo BA, Henry PJ. Stimulation of protease-activated receptor-2 inhibits airway eosinophilia, hyperresponsiveness and bronchoconstriction in a murine model of allergic inflammation. Br. J. Pharmacol. 144, 1100-1108 (2005).
36. Abey HT, Fairlie DP, Moffatt JD, Balzary RW, Cocks TM. Protease-activated receptor-2 peptides activate neurokinin-1 receptors in the mouse isolated trachea. J. Pharmacol Exp. Ther. 317, 598-605 (2006).
37. Kelso EB, Lockhart JC, Hembrough T et al. Therapeutic promise of proteinase-activated receptor-2 antagonism in joint inflammation. J. Pharmacol. Exp. Ther. 316, 1017-1024 (2006).
38. 1-antitrypsin deficiency. Lancet 365, 2225-2236 (2005).
39. Franciosi LG, Page CP, Celli BR et al. Markers of disease severity in chronic obstructive pulmonary disease. Pulm. Pharmacol. Ther. 19, 189-199 (2006).
40. Damiano VV, Tsang A, Kucich U et al. Immunolocalization of elastase in human emphysematous lungs. J. Clin. Invest. 78, 482-493 (1986).
41. Fox B, Bull TB, Guz A, Harris E, Tetley TD. Is neutrophil elastase associated with elastic tissue in emphysema? J. Clin. Pathol. 41, 435-440 (1988).
42. Zhu YK, Liu XD, Skold CM et al. Synergistic neutrophil elastase-cytokine interaction degrades collagen in three-dimensional culture. Am. J. Physiol. Lung Cell. Mol. Physiol. 281, L868-L878 (2001).
43. Shapiro SD, Goldstein NM, Houghton AM, Kobayashi DK, Kelley D, Belaaouaj A. Neutrophil elastase contributes to cigarette smoke-induced emphysema in mice. Am. J. Pathol. 163, 2329-2335 (2003).
44. Houghton AM, Quintero PA, Perkins DL et al. Elastin fragments drive disease progression in a murine model of emphysema. J. Clin. Invest. 116, 753-759 (2006).
45. Barnes PJ. Mediators of chronic obstructive pulmonary disease. Pharmacol. Rev. 56, 515-548 (2004).
46. Fischer BM, Voynow JA. Neutrophil elastase induces MUC5AC gene expression in airway epithelium via a pathway involving reactive oxygen species. Am. J. Respir. Cell Mol. Biol. 26, 447-452 (2002).
47. Postnov AA, Meurrens K, Weiler H et al. In vivo assessment of emphysema in mice by high resolution X-ray micro tomography. J. Microsc. 220, 70-75 (2005).
48. Fujie K, Shinguh Y, Yamazaki A, Hatanaka H, Okamoto M, Okuhara M. Inhibition of elastase-induced acute inflammation and pulmonary emphysema in hamsters by a novel neutrophil elastase inhibitor FR901277. Inflamm. Res. 48, 160-167 (1999).
49. Jansson AH, Smailagic A, Andersson AM et al. Evaluation of excised lung gas volume measurements in animals with genetic or induced emphysema. Respir. Physiol. Neurobiol. 150, 240-250 (2006).
50. Nishi Y, Boswell V, Ansari T, Piprawala F, Satchi S, Page CP. Elastase-induced changes in lung function: relationship to morphometry and effect of drugs. Pulm. Pharmacol. Ther. 16, 221-229 (2003).
51. Wright JL, Farmer SG, Churg A. Synthetic serine elastase inhibitor reduces cigarette smoke-induced emphysema in guinea pigs. Am. J. Respir. Crit. Care Med. 166, 954-960 (2002).
52. Belaaouaj A, McCarthy R, Baumann M et al. Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis. Nat. Med. 4, 615-618 (1998).
53. Hirche TO, Gaut JP, Heinecke JW, Belaaouaj A. Myeloperoxidase plays critical roles in killing Klebsiella pneumoniae and inactivating neutrophil elastase: effects on host defense. J. Immunol. 174, 1557-1565 (2005).
54. Overall CM, Kleifeld O. Tumour microenvironment - opinion: validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy. Nat. Rev. Cancer 6, 227-239 (2006).
55. Peterson JT. The importance of estimating the therapeutic index in the development of matrix metalloproteinase inhibitors. Cardiovasc. Res. 69, 677-687 (2006).
56. Rizvi NA, Humphrey JS, Ness EA et al. A Phase I study of oral BMS-275291, a novel nonhydroxamate sheddase-sparing matrix metalloproteinase inhibitor, in patients with advanced or metastatic cancer. Clin. Cancer Res. 10, 1963-1970 (2004).
57. Weathington NM, van Houwelingen AH, Noerager BD et al. A novel peptide CXCR ligand derived from extracellular matrix degradation during airway inflammation. Nat. Med. 12, 317-323 (2006).
58. Imai K, Dalal SS, Chen ES et al. Human collagenase (matrix metalloproteinase-1) expression in the lungs of patients with emphysema. Am. J. Respir Crit. Care Med. 163, 786-791 (2001).
59. Segura-Valdez L, Pardo A, Gaxiola M, Uhal BD, Becerril C, Selman M. Upregulation of gelatinases A and B, collagenases 1 and 2, and increased parenchymal cell death in COPD. Chest 117, 684-694 (2000).
60. Cataldo DD, Gueders M, Munaut C et al. Matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases mRNA transcripts in the bronchial secretions of asthmatics. Lab. Invest. 84, 418-424 (2004).
61. Culpitt SV, Rogers DF, Traves SL, Barnes PJ, Donnelly LE. Sputum matrix metalloproteases: comparison between chronic obstructive pulmonary disease and asthma. Respir. Med. 99, 703-710 (2005).
62. Nuttall RK, Sampieri CL, Pennington CJ, Gill SE, Schultz GA, Edwards DR. Expression analysis of the entire MMP and TIMP gene families during mouse tissue development. FEBS Lett. 563, 129-134 (2004).
63. D'Armiento J, Dalai SS, Okada Y, Berg RA, Chada K. Collagenase expression in the lungs of transgenic mice causes pulmonary emphysema. Cell 71, 955-961 (1992).
64. Foronjy RF, Okada Y, Cole R, D'Armiento J. Progressive adult-onset emphysema in transgenic mice expressing human MMP-1 in the lung. Am. J. Physiol. Lung Cell Mol. Physiol. 284, L727-L737 (2003).
65. Selman M, Montano M, Ramos C et al. Tobacco smoke-induced lung emphysema in guinea pigs is associated with increased interstitial collagenase. Am. J. Physiol. 271, L734-L743 (1996).
66. Wright JL, Churg A. Smoke-induced emphysema in guinea pigs is associated with morphometric evidence of collagen breakdown and repair. Am. J. Physiol. 268, L17-L20 (1995).
67. Gueders MM, Foidart JM, Noel A, Cataido DD. Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs in the respiratory tract: potential implications in asthma and other lung diseases. Eur. J. Pharmacol. 533, 133-144 (2006).
68. Finlay GA, O'Driscoll LR, Russell KJ et al. Matrix metalloproteinase expression and production by alveolar macrophages in emphysema. Am. J. Respir. Crit. Care Med. 156, 240-247 (1997).
69. Cataldo, D, Munaut C, Noel A et al. MMP-2- and MMP-9-finked gelatinolytic activity in the sputum from patients with asthma and chronic obstructive pulmonary disease. Int. Arch. Allergy Immunol. 123, 259-267 (2000).
70. Karwowski JK, Markezich A, Whitson J, Abbruzzese TA, Zarins CK, Dalman RL. Dose-dependent limitation of arterial enlargement by the matrix metalloproteinase inhibitor RS-113,456. J. Surg. Res. 87, 122-129 (1999).
71. Matsusaka H, Ide T, Matsushima S et al. Targeted deletion of matrix metalloproteinase 2 ameliorates myocardial remodeling in mice with chronic pressure overload. Hypertension 47, 711-717 (2006).
72. Kheradmand F, Rishi K, Werb Z. Signaling through the EGF receptor controls lung morphogenesis in part by regulating MT1-MMP-mediated activation of gelatinase A/MMP2. J. Cell. Sci. 115, 839-848 (2002).
73. Itoh T, Ikeda T, Gomi H, Nakao S, Suzuki T, Itohara S. Unaltered secretion of β-amyloid precursor protein in gelatinase A (matrix metalloproteinase 2)-deficient mice. J. Biol. Chem. 272, 22389-22392 (1997).
74. Corry DB, Rishi K, Kanellis J et al. Decreased allergic lung inflammatory cell egression and increased susceptibility to asphyxiation in MMP2-deficiency. Nat. Immunol. 3, 347-353 (2002).
75. Atkinson JJ, Holmbeck K, Yamada S, Birkedal-Hansen H, Parks WC, Senior RM. Membrane-type 1 matrix metalloproteinase is required for normal alveolar development. Dev. Dyn. 232, 1079-1090 (2005).
76. Dahlen B, Shute J, Howarth P Immunohistochemical localisation of the matrix metalloproteinases MMP-3 and MMP-9 within the air-ways in asthma. Thorax 54, 590-596 (1999).
77. Warner RL, Bhagavathula N, Nerusu KC et al. Matrix metalloproteinases in acute inflammation: induction of MMP-3 and MMP-9 in fibroblasts and epithelial cells following exposure to pro-inflammatory mediators in vitro. Exp. Mol. Pathol. 76, 189-195 (2004).
78. Bullard KM, Mudgett J, Scheuenstuhl H, Hunt TK, Banda MJ. Stromelysin-1-deficient fibroblasts display impaired contraction in vitro. J. Surg. Res. 84, 31-34 (1999).
79. Wang M, Qin X, Mudgett JS, Ferguson TA, Senior RM, Welgus HG. Matrix metalloproteinase deficiencies affect contact hypersensitivity: stromelysin-1 deficiency prevents the response and gelatinase B deficiency prolongs the response. Proc. Natl. Acad. Sci. USA 96, 6885-6889 (1999).
80. Warner RL, Beltran L, Younkin EM et al. Role of stromelysin 1 and gelatinase B in experimental acute lung injury. Am. J. Respir. Cell. Mol. Biol. 24, 537-544 (2001).
81. Vernooy JH, Lindeman JH, Jacobs JA, Hanemaaijer R, Wouters EF. Increased activity of matrix metalloproteinase-8 and matrix metalloproteinase-9 in induced sputum from patients with COPD. Chest 126, 1802-1810 (2004).
82. Betsuyaku T, Nishimura M, Takeyabu K et al. Neutrophil granule proteins in bronchoalveolar lavage fluid from subjects with subclinical emphysema. Am. J. Respir. Crit. Care Med. 159, 1985-1991 (1999).
83. Prikk K, Maisi P, Pirila E et al. Airway obstruction correlates with collagenase-2 (MMP-8) expression and activation in bronchial asthma. Lab. Invest. 82, 1535-1545 (2002).
84. Gueders MM, Balbin M, Rocks N et al. Matrix metalloproteinase-8 deficiency promotes granulocytic allergen-induced airway inflammation. J. Immunol. 175, 2589-2597 (2005).
85. Balbin M, Fueyo A, Tester AM et al. Loss of collagenase-2 confers increased skin tumor susceptibility to male mice. Nat. Genet. 35, 252-257 (2003).
86. Atkinson JJ, Senior RM. Matrix metalloproteinase-9 in lung remodeling. Am. J. Respir. Cell. Mol. Biol. 28, 12-24 (2003).
87. Russell RE, Culpitt SV, DeMatos C et al. Release and activity of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 by alveolar macrophages from patients with chronic obstructive pulmonary disease. Am. J. Respir. Cell. Mol. Biol. 26, 602-609 (2002).
88. Parks WC, Shapiro SD. Matrix metalloproteinases in lung biology. Respir Res. 2, 10-19 (2001).
89. Churg A, Wright JL. Proteases and emphysema. Curr. Opin. Pulm. Med. 11, 153-159 (2005).
90. Zheng T Zhu Z, Wang Z et al. Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase- and cathepsin-dependent emphysema. J. Clin. Invest. 106, 1081-1093 (2000).
91. Lanone S, Zheng T, Zhu Z et al. Overlapping and enzyme-specific contributions of matrix metalloproteinases-9 and -12 in IL-13-induced inflammation and remodeling. J. Clin. Invest. 110, 463-474 (2002).
92. Boutten A, Bonay M, Laribe S et al. Decreased expression of interleukin 13 in human lung emphysema. Thorax 59, 850-854 (2004).
93. Renckens R, Roelofs JJ, Florquin S et al. Matrix metalloproteinase-9 deficiency impairs host defense against abdominal sepsis. J. Immunol. 176, 3735-3741 (2006).
94. Demedts IK, Brusselle GG, Bracke KR, Vermaelen KY, Pauwels RA. Matrix metalloproteinases in asthma and COPD. Curr. Opin. Pharmacol. 5, 257-263 (2005).
95. McMillan SJ, Kearley J, Campbell JD et al. Matrix metalloproteinase-9 deficiency results in enhanced allergen-induced airway inflammation. J. Immunol. 172, 2586-2594 (2004).
96. Cataldo DD, Tournoy KG, Vermaelen K et al. Matrix metalloproteinase-9 deficiency impairs cellular infiltration and bronchial hyperresponsiveness during allergen-induced airway inflammation. Am. J. Pathol. 161, 491-498 (2002).
97. Vermaelen KY, Cataldo D, Tournoy K et al. Matrix metalloproteinase-9-mediated dendritic cell recruitment into the airways is a critical step in a mouse model of asthma. J. Immunol. 171, 1016-1022 (2003).
98. Corry DB, Kiss A, Song LZ et al. Overlapping and independent contributions of MMP2 and MMP9 to lung allergic inflammatory cell egression through decreased CC chemokines. FASEB J. 18, 995-997 (2004).
99. Lim DH, Cho JY, Miller M, McElwain K, McElwain S, Broide DH. Reduced peribronchial fibrosis in allergen-challenged MMP-9-deficient mice. Am. J. Physiol. Lung Cell. Mol. Physiol. 291, L265-L271 (2006).
100. Gronski TJ Jr, Martin RL, Kobayashi DK et al. Hydrolysis of a broad spectrum of extracellular matrix proteins by human macrophage elastase. J. Biol. Chem. 272, 12189-12194 (1997).
101. Xie S, Issa R, Sukkar MB et al. Induction and regulation of matrix metalloproteinase-12 in human air-way smooth muscle cells. Respir. Res. 6, 148 (2005).
102. Lavigne MC, Thakker P, Gunn J. et al. Human bronchial epithelial cells express and secrete MMP-12. Biochem. Biophys. Res. Commun. 324, 534-546 (2004).
103. Lavigne MC, Eppihimer MJ. Cigarette smoke condensate induces MMP-12 gene expression in airway-like epithelia. Biochem. Biophys. Res. Commun. 330, 194-203 (2005).
104. Molet S, Belleguic C, Lena H et al. Increase in macrophage elastase (MMP-12) in lungs from patients with chronic obstructive pulmonary disease. Inflamm. Res. 54, 31-36 (2005).
105. Demedts IK, Morel-Montero A, Lebecque S et al. Elevated MMP-12 protein levels in induced sputum from patients with COPD. Thorax 61, 196-201 (2006).
106. Hauramaki RD, Kobayashi DK, Senior RM, Shapiro SD. Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice. Science 277, 2002-2004 (1997).
107. Churg A, Zay K, Shay S et al. Acute cigarette smoke-induced connective tissue breakdown requires both neutrophils and macrophage metalloelastase in mice. Am. J. Respir. Cell. Mol. Biol. 27, 368-374 (2002).
108. Houghton AM, Grisolano JL, Baumann ML et al. Macrophage elastase (matrix metalloproteinase-12) suppresses growth of lung in metastases. Cancer Res. 66, 6149-6155 (2006).
109. Karnaukhova E, Ophir Y, Golding B. Recombinant human α-1 proteinase inhibitor: towards therapeutic use. Amino Acids 30, 317-332 (2006).
110. Attucci S, Gauthier A, Korkmaz B et al. EPI-hNE4, a proteolysis-resistant inhibitor of human neutrophil elastase and potential anti-inflammatory drug for treating cystic fibrosis. J. Pharmacol. Exp. Ther. 318, 803-809 (2006).
111. Williams SE, Brown TI, Roghanian A, Sallenave JM. SLPI and elafin: one glove, many fingers. Clin. Sci. (Lond.) 110, 21-35 (2006).
112. Overall CM, Lopez-Otin C. Strategies for MMP inhibition in cancer: innovations for the post-trial era. Nat. Rev. Cancer 2, 657-672 (2002).
113. Ito K, Ito M, Elliott WM et al. Decreased histone deacetylase activity in chronic obstructive pulmonary disease. N. Engl. J. Med. 352, 1967-1976 (2005).
114. Choe KH, Taraseviciene-Stewart L, Scerbavicius R, Gera L, Tuder RM, Voelkel NF. Methylprednisolone causes matrix metalloproteinase-dependent emphysema in adult rats. Am. J. Respir. Crit. Care Med. 167, 1516-1521 (2003).
115. Lee YM, Park JS, Hwang JH et al. High-resolution CT findings in patients with near-fatal asthma: comparison of patients with mild-to-severe asthma and normal control subjects and changes in airway abnormalities following steroid treatment. Chest 126, 1840-1848 (2004).
116. Yilmaz S, Ekici A, Ekici M, Keles H. High-resolution computed tomography findings in elderly patients with asthma. Eur. J. Radiol. 59, 238-243 (2006).
117. Leclerc O, Lagente V, Planquois JM et al. Involvement of MMP-12 and phosphodiesterase type 4 in cigarette smoke-induced inflammation in mice. Eur. Respir. J. 27, 1102-1109 (2006).
118. Delany AM, Jeffrey JJ, Rydziel S, Canalis E. Cortisol increases interstitial collagenase expression in osteoblasts by post-transcriptional mechanisms. J. Biol. Chem. 270, 26607-26612 (1995).
119. Kim HJ, Zhao H, Kitaura H et al. Glucocorticoids suppress bone formation via the osteoclast. J. Clin. Invest. 116, 2152-2160 (2006).
120. Carver JE, Galloway VA, Robinson C. Inhibition of gelatinase activity in human airway epithelial cells and fibroblasts by dexamethasone and beclomethasone. Br. J. Pharmacol. 127, 1119-1128 (1999).
121. Martin-Chouly CA, Astier A, Jacob C, Pruniaux MP, Bertrand C, Lagente V. Modulation of matrix metalloproteinase production from human lung fibroblasts by type 4 phosphodiesterase inhibitors. Life Sci. 75, 823-840 (2004).
122. Zaczynska E, Gabra BH, Sirois P. Bradykinin stimulates MMP-2 production in guinea pig tracheal smooth muscle cells. Inflammation 27, 307-315 (2003).
123. 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. 146, 2724-2729 (1991).
124. Mautino G, Oliver N, Chanez P, Bousquet J, Capony F. Increased release of matrix metalloproteinase-9 in bronchoalveolar lavage fluid and by alveolar macrophages of asthmatics. Am. J. Respir. Cell. Mol. Biol. 17, 583-591 (1997).
125. Shapiro SD, Kobayashi DK, Ley TJ. Cloning and characterization of a unique elastolytic metalloproteinase produced by human alveolar macrophages. J. Biol. Chem. 268, 23824-23829 (1993).
126. Spina D. Phosphodiesterase-4 inhibitors in the treatment of inflammatory lung disease. Drugs 63, 2575-2594 (2003).
127. Compton CH, Gubb J, Nieman R et al. Cilomilast, a selective phosphodiesterase-4 inhibitor for treatment of patients with chronic obstructive pulmonary disease: a randomised, dose-ranging study. Lancet 358, 265-270 (2001).
128. Rabe KF, Bateman ED, O'Donnell D, Witte S, Bredenbroker D, Bethke TD. Roflumilast - an oral anti-inflammatory treatment for chronic obstructive pulmonary disease: a randomised controlled trial. Lancet 366, 563-571 (2005).
129. Rennard SI, Schachter N, Strek M, Rickard K, Amit O. Cilomilast for COPD: results of a 6-month, placebo-controlled study of a potent, selective inhibitor of phosphodiesterase 4. Chest 129, 56-66 (2006).
130. Gamble E, Grootendorst DC, Brightling CE et al. Antiinflammatory effects of the phosphodiesterase-4 inhibitor cilomilast (ariflo) in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 168, 976-982 (2003).
131. Grootendorst DC, Gauw SA, Sterk PJ et al. Treatment with PDE4 inhibitor Roflumilast reduces sputum neutrophil and eosinophil numbers in patients with COPD. Proc. Am. Thorac. Soc. 2, A543 (2005).
132. Martorana PA, Beume R, Lucattelli M, Wallin L, Lungarella G. Roflumilast fully prevents emphysema in mice chronically exposed to cigarette smoke. Am. J. Respir. Crit. Care Med. 172, 848-853 (2005).
133. Bundschuh DS, Eltze M, Barsig J, Wollin L, Hatzelmann A, Beume R. In vivo efficacy in airway disease models of roflumilast, a novel orally active PDE4 inhibitor. J. Pharmacol. Exp. Ther. 297, 280-290 (2001).
134. Spond J, Chapman R, Fine J et al. Comparison of PDE 4 inhibitors, rolipram and SB 207499 (ariflo), in a rat model of pulmonary neutrophilia. Pulm. Pharmacol. Ther. 14, 157-164 (2001).
135. Kumar RK, Herbert C, Thomas PS et al. Inhibition of inflammation and remodeling by roflumilast and dexamethasone in murine chronic asthma. J. Pharmacol. Exp. Ther. 307, 349-355 (2003).
136. Takahashi S, Ito A, Nagino M, Mori Y, Xie B, Nagase H. Cyclic adenosine 3′,5′-monophosphate suppresses interleukin 1-induced synthesis of matrix metalloproteinases but not of tissue inhibitor of metalloproteinases in human uterine cervical fibroblasts. J. Biol. Chem. 266, 19894-19899 (1991).
137. Kohyama T, Liu X, Zhu YK et al. Phosphodiesterase 4 inhibitor cilomilast inhibits fibroblast-mediated collagen gel degradation induced by tumor necrosis factor-α and neutrophil elastase. Am. J. Respir. Cell. Mol. Biol. 27, 487-494 (2002).
138. Liu X, Ostrom RS, Insel PA. cAMP-elevating agents and adenylyl cyclase overexpression promote an antifibrotic phenotype in pulmonary fibroblasts. Am. J. Physiol. Cell. Physiol. 286, C1089-C1099 (2004).
139. Jones NA, Boswell-Smith V, Lever R, Page CP. The effect of selective phosphodiesterase isoenzyme inhibition on neutrophil function in vitro. Pulm. Pharmacol. Ther. 18, 93-101 (2005).
140. Hatzelmann A, Schudt C. Anti-inflammatory and immunomodulatory potential of the novel PDE4 inhibitor roflumilast in vitro. J. Pharmacol. Exp. Ther. 297, 267-279 (2001).
141. + T-lymphocytes. Mol. Pharmacol. 66(6), 1679-1689 (2004).
142. Barnes PJ, Stockley RA. COPD: current therapeutic interventions and future approaches. Eur. Respir. J. 25, 1084-1106 (2005).
143. + T-lymphocytes. Mol. Pharmacol. 66, 1679-1689 (2004).
144. Boswell-Smith V, Spina D, Oxford AW, Comer MB, Seeds EA, Page CP. The pharmacology of two novel long-acting phosphodiesterase 3/4 inhibitors, RPL554 [9,10-dimethoxy-2 (2,4,6-trimethylphenylimino)- 3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H- pyrimido[6,1-a]isoquinolin-4-one] and RPL565 [6,7-dihydro-2-(2, 6-diisopropylphenoxy)-9,10-dimethoxy-4H-pyrimido[6,1-a] isoquinolin-4-one]. J. Pharmacol. Exp. Ther. 318, 840-848 (2006).
145. Selman M, Cisneros-Lira J, Gaxiola M et al. Matrix metalloproteinases inhibition attenuates tobacco smoke-induced emphysema in Guinea pigs. Chest 123, 1633-1641 (2003).
146. Ma D, Jiang Y, Chen F et al. Selective inhibition of matrix metalloproteinase isozymes and in vivo protection against emphysema by substituted γ-keto carboxylic acids. J. Med. Chem. 49, 456-458 (2006).
147. Clark JM, Abraham WM, Fishman CE et al. Tryptase inhibitors block allergen-induced airway and inflammatory responses in allergic sheep. Am. J. Respir. Crit. Care Med. 152, 2076-2083 (1995).
148. Wright CD, Havill AM, Middleton SC et al. Inhibition of allergen-induced pulmonary responses by the selective tryptase inhibitor 1,5-bis-[4-[(3-carbamimidoyl-benzenesulfonylamino)-methyll-phenoxy]- pentane (AMG-126737). Biochem. Pharmacol. 58, 1989-1996 (1999).
149. Oh SW, Pae CI, Lee DK et al. Tryptase inhibition blocks airway inflammation in a mouse asthma model. J. Immunol. 168, 1992-2000 (2002).
150. Costanzo Mi, Yabui SC, Almond HR Jr. et al. Potent, small-molecule inhibitors of human mast cell tryptase. Antiasthmatic action of a dipeptide-based transition-state analogue containing a benzothiazole ketone. J. Med. Chem. 46, 3865-3876 (2003).
151. Chen CL, Wang SD, Zeng ZY et al. Serine protease inhibitors nafamostat mesilate and gabexate mesilate attenuate allergen-induced airway inflammation and eosinophilia in a murine model of asthma. J. Allergy Clin. Immunol. 118, 105-112 (2006).
152. Sperandio D, Tai VW, Lohman J et al. Novel, potent, selective, and orally bioavailable human βaII-tryptase inhibitors. Bioorg. Med. Chem. Lett. 16, 4085-4089 (2006).
153. Shinguh Y, Yamazaki A, Inamura N et al. Biochemical and pharmacological characterization of FR134043, a novel elastase inhibitor. Eur. J. Pharmacol. 345, 299-308 (1998).
154. Kuraki T, Ishibashi M, Takayama M, Shiraishi M, Yoshida M. A novel oral neutrophil elastase inhibitor (ONO-6818) inhibits human neutrophil elastase-induced emphysema in rats. Am. J. Respir. Crit. Care Med. 166, 496-500 (2002).
155. Luisetti M, Sturani C, Sella D et al. MR889, a neutrophil elastase inhibitor, in patients with chronic obstructive pulmonary disease: a double-blind, randomized, placebo-controlled clinical trial. Eur. Respir. J. 91 1482-1486 (1996).
156. Pemberton PA, Cantwell JS, Kim KM et al. An inhaled matrix metalloprotease inhibitor prevents cigarette smoke-induced emphysema in the mouse. COPD 2, 303-310 (2005).
157. Tan RJ, Fattman CL, Niehouse LM et al. Matrix metalloproteinases promote inflammation and fibrosis in asbestos-induced lung injury in mice. Am. J. Respir. Cell Mol. Biol. 35, 289-297 (2006).