Antiproteases and retinoids for treatment of chronic obstructive pulmonary disease

Expert Opinion on Therapeutic Patents

Volumn 13, Issue 9, 2003, Pages 1345-1372

  Donnelly, Louise E ^a   Rogers, Duncan F ^a  

^a NATIONAL HEART AND LUNG INSTITUTE   (United Kingdom)

Author keywords

Airway(s); All trans retinoic acid (ATRA); Cathepsin; Chronic obstructive pulmonary disease (COPD); Elastase; Emphysema; Matrix metalloproteinase (MMP); Mucus hypersecretion; Protease; Retinoid

Indexed keywords

ALPHA 1 ANTITRYPSIN; AMIDE; BETA AMINO ACID; BRONCHODILATING AGENT; CARBOXYLIC ACID DERIVATIVE; CHOLINERGIC RECEPTOR BLOCKING AGENT; CYSTEINE PROTEINASE INHIBITOR; ELAFIN; GLUCOCORTICOID; GUANIDINE DERIVATIVE; HYDROXAMIC ACID DERIVATIVE; LACTAM DERIVATIVE; MATRIX METALLOPROTEINASE INHIBITOR; NITRILE; OXADIAZOLE DERIVATIVE; PIPERAZINE DERIVATIVE; PIPERIDINE DERIVATIVE; POLYPEPTIDE; PROTEINASE; PROTEINASE INHIBITOR; RESPITIN; RETINOIC ACID DERIVATIVE; RETINOIC ACID RECEPTOR ALPHA; RETINOIC ACID RECEPTOR ALPHA BLOCKING AGENT; RETINOIC ACID RECEPTOR GAMMA; RETINOIC ACID RECEPTOR GAMMA STIMULATING AGENT; RETINOID DERIVATIVE; SERINE PROTEINASE INHIBITOR; SIVELESTAT; THEOPHYLLINE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

CAUSE OF DEATH; CHRONIC OBSTRUCTIVE LUNG DISEASE; DISEASE SEVERITY; DRUG SPUTUM LEVEL; DRUG STRUCTURE; ENZYME INHIBITION; HUMAN; INCIDENCE; NONHUMAN; PATENT; PATHOPHYSIOLOGY; RESPIRATORY TRACT INFLAMMATION; REVIEW; TISSUE REPAIR; UNITED KINGDOM; UNITED STATES;

EID: 0141851910     PISSN: 13543776     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543776.13.9.1345     Document Type: Review

References (150)

1. TURINO GM: The origins of a concept: the protease-antiprotease imbalance hypothesis. Chest (2002) 122:1058-1060.
2. HOGG JC, SENIOR RM: Chronic obstructive pulmonary disease - part 2: pathology and biochemistry of emphysema. Thorax (2002) 57:830-834.
3. BARNES PJ: New concepts in chronic obstructive pulmonary disease. Ann. Rev. Med. (2003) 54:113-129.
4. CULPITT SV, ROGERS DF: Evaluation of current pharmacotherapy of chronic obstructive pulmonary disease. Expert Opin. Pharmacother. (2000) 1:1007-1020.
5. BARNES PJ: Therapy of chronic obstructive pulmonary disease. Pharmacol. Ther. (2003) 97:87-94.
6. DONNELLY LE, ROGERS DF: Therapy for COPD in the 21st Century. Drugs (2003) 63(19).
7. SHAPIRO SD: Proteinases in chronic obstructive pulmonary disease. Biochem. Soc. Trans. (2002) 30:98-102.
8. MASSARO D, DE CARLO MG: Retinoids, alveolus formation, and alveolar deficiency: clinical implications. Am. J. Respir. Cell Mol. Biol. (2003) 28:271-274.
9. NORMAN P: Pulmonary Diseases. Disease Trend and Market Opportunities. Financial Times Business Ltd, London (1999).
10. NATIONAL HEART, LUNG & BLOOD INST. WORLD HEALTH ORGANIZATION: Global Initiative for Chronic Obstructive Lung Disease. National Institutes of Health (2001) (Publication number 2701).
11. HURD S: The impact of COPD on lung health worldwide: epidemiology and incidence. Chest (2000) 117:1S-4S.
12. BRITTON M: The burden of COPD in the UK: results from the Confronting COPD survey. Respir. Med. (2003) 97(Suppl.C):S71-S79.
13. MANNINO DM: COPD: epidemiology, prevalence, morbidity and mortality, and disease heterogeneity. Chest (2002) 121:121S-126S.
14. HALPERN MT, STANFORD RH, BORKER R: The burden of COPD in the USA: results from the confronting COPD survey. Respir. Med. (2003) 97(Suppl.C):S81-S89.
15. SULLIVAN SD, RAMSEY SD, LEE TA: The economic burden of COPD. Chest (2000) 117:5S-9S.
16. FLETCHER C, PETO R: The natural history of chronic airflow obstruction. Br. Med. J. (1977) 1:1645-1648.
17. ANTHONISEN NR, CONNETT JE, KILEY JP et al.: Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1. The Lung Health Study. JAMA (1994) 272:1497-1505.
18. ROGERS DF: Mucus pathophysiology in COPD: differences to asthma, and pharmacotherapy. Monaldi Arch. Chest Dis. (2000) 55:324-332.
19. JEFFERY PK: Remodeling in asthma and chronic obstructive lung disease. Am. J. Respir. Crit. Care Med. (2001) 164:S28-S38.
20. MAESTRELLI P, SAETTA M, MAPP CE, FABBRI LM: Remodeling in response to infection and injury. Airway inflammation and hypersecretion of mucus in smoking subjects with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. (2001) 164:S76-S80.
21. TETLEY TD: Macrophages and the pathogenesis of COPD. Chest (2002) 121:156S-159S.
22. STOCKLEY RA: Neutrophils and the pathogenesis of COPD. Chest (2002) 121:151S-155S.
23. STOCKLEY RA: Proteases and antiproteases. Novartis Found. Symp. (2001) 234:189-199.
24. JEFFERY PK: Comparison of the structural and inflammatory features of COPD and asthma. Giles F Filley Lecture. Chest (2000) 117(5:Suppl.1):251S-260S.
25. BARNES PJ: Mechanisms in COPD: differences from asthma. Chest (2000) 117:10S-14S.
26. BARNES PJ: Inhaled corticosteroids are not beneficial in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. (2000) 161:342-344.
27. CALVERLEY PM: Inhaled corticosteroids are beneficial in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. (2000) 161:341-342.
28. STARCHER BC: Lung elastin and matrix. Chest (2000) 117-229S-234S.
29. FORONJY R, D'ARMIENTO J: The role of collagenase in emphysema. Respir. Res. (2001) 2:348-352.
30. OHBAYASHI H: Matrix metalloproteinases in lung diseases. Curr. Protein Pept. Sci. (2002) 3:409-421.
31. SHIOMI T, OKADA Y, FORONJY R et al.: Emphysematous changes are caused by degradation of Type III collagen in transgenic mice expressing MMP-1. Exp. Lung Res. (2003) 29:1-15.
32. PARKS WC, SHAPIRO SD: Matrix metalloproteinases in lung biology. Respir. Res. (2001) 2:10-19.
33. STERNLICHT MD, WERB Z: How matrix metalloproteinases regulate cell behavior. Ann. Rev. Cell Dev. Biol. (2001) 17:463-516.
34. KAJITA M, ITOH Y, CHIBA T et al.: Membrane-type 1 matrix metalloproteinase cleaves CD44 and promotes cell migration. J. Cell Biol. (2001) 153:893-904.
35. WALLACE AM, SANDFORD AJ: Genetic polymorphisms of matrix metalloproteinases: functional importance in the development of chronic obstructive pulmonary disease? Am. J. Pharmacogenomics (2002) 2:167-175.
36. 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 (1996) 271:L734-L743.
37. 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. (2003) 284:L727-L737.
38. 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. (1997) 156:240-247.
39. 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 (2000) 117:684-694.
40. 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. (2001) 163:786-791.
41. JOOS L, HE JQ, SHEPHERDSON MB et al.: The role of matrix metalloproteinase polymorphisms in the rate of decline in lung function. Hum. Mol. Genet. (2002) 11:569-576.
42. 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. (1999) 159:1985-1991.
43. FINLAY GA, RUSSELL KJ, MCMAHON KJ et al.: Elevated levels of matrix metalloproteinases in bronchoalveolar lavage fluid of emphysematous patients. Thorax (1997) 52:502-506.
44. OPDENAKKER G, VAN DEN STEEN PE et al.: Gelatinase B functions as regulator and effector in leukocyte biology. J. Leukoc. Biol. (2001) 69:851-859.
45. 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. (2002) 26:602-609.
46. MINEMATSU N, NAKAMURA H, TATENO H, NAKAJIMA T, YAMAGUCHI K: Genetic polymorphism in matrix metalloproteinase-9 and pulmonary emphysema. Biochem. Biophys. Res. Commun. (2001) 289:116-119.
47. SHAPIRO SD: Elastolytic metalloproteinases produced by human mononuclear phagocytes. Potential roles in destructive lung disease. Am. J. Respir. Crit. Care Med. (1994) 150:S160-S164.
48. BUSIEK DF, BARAGI V, NEHRING LC, PARKS WC, WELGUS HG: Matrilysin expression by human mononuclear phagocytes and its regulation by cytokines and hormones. J. Immunol. (1995) 154:6484-6491.
49. WILSON CL, MATRISIAN LM: Matrilysin: an epithelial matrix metalloproteinase with potentially novel functions. Int. J. Biochem. Cell Biol. (1996) 28:123-136.
50. SU WY, JASKOT RH, RICHARDS J et al.: Induction of pulmonary matrilysin expression by combustion and ambient air particles. Am. J. Physiol. Lung Cell Mol. Physiol. (2000) 279:L152-L160.
51. COSGROVE GP, SCHWARZ MI, GERACI MW, BROWN KK, WORTHEN GS: Overexpression of matrix metalloproteinase-7 in pulmonary fibrosis. Chest (2002) 121:25S-26S.
52. HAUTAMAKI RD, KOBAYASHI DK, SENIOR RM, SHAPIRO SD: Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice. Science (1997) 277:2002-2004.
53. 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. (1997) 272:12189-12194.
54. WANG Z, ZHENG T, ZHU Z et al.: Interferon-γ induction of pulmonary emphysema in the adult murine lung. J. Exp. Med. (2000) 192:1587-1600.
55. CHURG A, WANG RD, TAI H et al.: Macrophage metalloelastase mediates acute cigarette smoke-induced inflammation via tumor necrosis factor-alpha release. Am. J. Respir. Crit. Care Med. (2003) 167:1083-1089.
56. OHNISHI K, TAKAGI M, KUROKAWA Y, SATOMI S, KONTTINEN YT: Matrix metalloproteinase-mediated extracellular matrix protein degradation in human pulmonary emphysema. Lab. Invest. (1998) 78:1077-1087.
57. JOOS L, PARE PD, SANDFORD AJ: Genetic risk factors of chronic obstructive pulmonary disease. Swiss. Med. Wkly (2002) 132:27-37.
58. CAUGHEY GH: Serine proteinases of mast cell and leukocyte granules. A league of their own. Am. J. Respir. Crit. Care Med. (1994) 150:S138-S142.
59. HEDSTROM L: Serine protease mechanism and specificity. Chem. Rev. (2002) 102:4501-4524.
60. BODE W, MEYER E Jr, POWERS JC: Human leukocyte and porcine pancreatic elastase: X-ray crystal structures, mechanism, substrate specificity, and mechanism-based inhibitors. Biochemistry (1989) 28:1951-1963.
61. LEE WL, DOWNEY GP: Leukocyte elastase: physiological functions and role in acute lung injury. Am. J. Respir. Crit. Care Med. (2001) 164:896-904.
62. SHAPIRO SD: Neutrophil elastase: path clearer, pathogen killer, or just pathologic? Am. J. Respir. Cell Mol. Biol. (2002) 26:266-268.
63. BELAAOUAJ A: Neutrophil elastase-mediated killing of bacteria: lessons from targeted mutagenesis. Microbes Infect. (2002) 4:1259-1264.
64. TKALCEVIC J, NOVELLI M, PHYLACTIDES M, IREDALE JP, SEGAL AW, ROES J: Impaired immunity and enhanced resistance to endotoxin in the absence of neutrophil elastase and cathepsin G. Immunity (2000) 12:201-210.
65. 1-antitrypsin deficiency. Scand. J. Clin. Lab. Invest. (1963) 15:132-140.
66. MAHADEVA R, SHAPIRO SD: Experimental animal models of pulmonary emphysema. Thorax (2002) 57:908-914.
67. LUCEY EC, STONE PJ, BREUER R et al.: Effect of combined human neutrophil cathepsin G and elastase on induction of secretory cell metaplasia and emphysema in hamsters, with in vitro observations on elastolysis by these enzymes. Am. Rev. Respir. Dis. (1985) 132:362-366.
68. SOMMERHOFF CP, NADEL JA, BASBAUM CB, CAUGHEY GH: Neutrophil elastase and cathepsin G stimulate secretion from cultured bovine airway gland serous cells. J. Clin. Invest. (1990) 85:682-689.
69. FISCHER BM, CUELLAR JG, DIEHL ML et al.: Neutrophil elastase increases MUC4 expression in normal human bronchial epithelial cells. Am. J. Physiol. Lung Cell Mol. Physiol. (2003) 284:L671-L679.
70. 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. (2002) 26:447-452.
71. ROGERS DF: The airway goblet cell. Int. J. Biochem. Cell Biol. (2003) 35:1-6.
72. LE BARILLEC K, SI-TAHAR M, BALLOY V, CHIGNARD M: Proteolysis of monocyte CD14 by human leukocyte elastase inhibits lipopolysaccharide-mediated cell activation. J. Clin. Invest. (1999) 103:1039-1046.
73. VANDIVIER RW, FADOK VA, HOFFMANN PR et al.: Elastase-mediated phosphatidylserine receptor cleavage impairs apoptotic cell clearance in cystic fibrosis and bronchiectasis. J. Clin. Invest. (2002) 109:661-670.
74. GROSSO LE, SCOTT M: Peptide sequences selected by BA4, a tropoelastin-specific monoclonal antibody, are ligands for the 67-kDa bovine elastin receptor. Biochemistry (1993) 32:13369-13374.
75. UEMURA, Y. OKAMOTO K: Elastin-derived peptide induces monocyte chemotaxis by increasing intracellular cyclic GMP level and activating cyclic GMP dependent protein kinase. Biochem. Mol. Biol. Int. (1997) 41:1085-1092.
76. BANGALORE N, TRAVIS J, ONUNKA VC, POHL J, SHAFER WM: Identification of the primary antimicrobial domains in human neutrophil cathepsin G. J. Biol. Chem. (1990) 265:13584-13588.
77. + flux. Nature (2002) 416:291-297.
78. ROOS D, WINTERBOURN CC: Immunology. Lethal weapons. Science (2002) 296:669-671.
79. MACIVOR DM, SHAPIRO SD, PHAM CT, BELAAOUAJ A, ABRAHAM SN, LEY TJ: Normal neutrophil function in cathepsin G-deficient mice. Blood (1999) 94:4282-4293.
80. LE BARILLEC K, PIDARD D, BALLO YV, CHIGNARD M: Human neutrophil cathepsin G down-regulates LPS-mediated monocyte activation through CD14 proteolysis. J. Leukoc. Biol. (2000) 68:209-215.
81. BANK U, KUPPER B, ANSORGE S: Inactivation of interleukin-6 by neutrophil proteases at sites of inflammation. Protective effects of soluble IL-6 receptor chains. Adv. Exp. Med. Biol. (2000) 477:431-437.
82. SHAMAMIAN P, SCHWARTZ JD, POCOCK BJ et al.: Activation of progelatinase A (MMP-2) by neutrophil elastase, cathepsin G, and proteinase-3: a role for inflammatory cells in tumor invasion and angiogenesis. J. Cell Physiol. (2001) 189:197-206.
83. NUFER O, CORBETT M, WALZ A: Amino-terminal processing of chemokine ENA-78 regulates biological activity. Biochemistry (1999) 38:636-642.
84. SAMBRANO GR, HUANG W, FARUQI T, MAHRUS S, CRAIK C, COUGHLIN SR: Cathepsin G activates protease-activated receptor-4 in human platelets. J. Biol. Chem. (2000) 275:6819-6823.
85. OWEN CA, CAMPBELL EJ: The cell biology of leukocyte-mediated proteolysis. J. Leukoc. Biol. (1999) 65:137-150.
86. CAMPBELL EJ, CAMPBELL MA, OWEN CA: Bioactive proteinase 3 on the cell surface of human neutrophils: quantification, catalytic activity, and susceptibility to inhibition. J. Immunol. (2000) 165:3366-3374.
87. RAO NV, WEHNER NG, MARSHALL BC, GRAY WR, GRAY BH, HOIDAL JR: Characterization of proteinase-3 (PR-3), a neutrophil serine proteinase. Structural and functional properties. J. Biol. Chem. (1991) 266:9540-9548.
88. KAO RC, WEHNER NG, SKUBITZ KM, GRAY BH, HOIDAL JR: Proteinase 3. A distinct human polymorphonuclear leukocyte proteinase that produces emphysema in hamsters. J. Clin. Invest (1988) 82:1963-1973.
89. PEZZATO E, DONA M, SARTOR L et al.: Proteinase-3 directly activates MMP-2 and degrades gelatin Matrigel; differential inhibition by (-)epigallocatechin-3-gallate. J. Leukoc. Biol. (2003) 74:88-94.
90. CHAPMAN HA, RIESE RJ, SHI GP: Emerging roles for cysteine proteases in human biology. Ann. Rev. Physiol. (1997) 59:63-88.
91. WOLTERS PJ, CHAPMAN HA: Importance of lysosomal cysteine proteases in lung disease. Respir. Res. (2000) 1:170-177.
92. BUHLING F, FENGLER A, BRANDT W, WELTE T, ANSORGE S, NAGLER DK: Review: novel cysteine proteases of the papain family. Adv. Exp. Med. Biol. (2000) 477:241-254.
93. TAKAHASHI H, ISHIDOH K, MUNO D et al.: Cathepsin L activity is increased in alveolar macrophages and bronchoalveolar lavage fluid of smokers. Am. Rev. Respir. Dis. (1993) 147:1562-1568.
94. TAKEYABU K, BETSUYAKU T, NISHIMURA M et al.: Cysteine proteinases and cystatin C in bronchoalveolar lavage fluid from subjects with subclinical emphysema. Eur. Respir. J. (1998) 12:1033-1039.
95. TAGGART CC, LOWE GJ, GREENE CM et al.: Cathepsin B, L, S cleave and inactivate secretory leucoprotease inhibitor. J. Biol. Chem. (2001) 276:33345-33352.
96. PADILLA ML, GALICKI NI, KLEINERMAN J, ORLOWSKI M, LESSER M: High cathepsin B activity in alveolar macrophages occurs with elastase-induced emphysema but not with bleomycin-induced pulmonary fibrosis in hamsters. Am. J. Pathol. (1988) 131:92-101.
97. SCHWAIBLMAIR M, VOGELMEIER C: Alpha 1-antitrypsin. Hope on the horizon for emphysema sufferers? Drugs Aging (1998) 12:429-440.
98. STOCKLEY RA, BAYLEY DL, UNSAL I, DOWSON LJ: The effect of augmentation therapy on bronchial inflammation in alpha1-antitrypsin deficiency. Am. J. Respir. Crit. Care Med. (2002) 165:1494-1498.
99. 1-antitrypsin, Respitin. Chest (2002) 122:66-74.
100. MITSUHASHI H, ASANO S, NONAKA T, HAMAMURA I, MASUDA K, KIYOKI M: Administration of truncated secretory leukoprotease inhibitor ameliorates bleomycin-induced pulmonary fibrosis in hamsters. Am. J. Respir. Crit. Care Med. (1996) 153:369-374.
101. MITSUHASHI H, ASANO S, NONAKA T, MASUDA K, KIYOKI M: Potency of truncated secretory leukoprotease inhibitor assessed in acute lung injury models in hamsters. J. Pharmacol. Exp. Ther. (1997) 282:1005-1010.
102. TREMBLAY GM, VACHON E, LAROUCHE C, BOURBONNAIS Y: Inhibition of human neutrophil elastase-induced acute lung injury in hamsters by recombinant human pre-elafin (trappin-2). Chest (2002) 121:582-588.
103. OHBAYASHI H: Neutrophil elastase inhibitors as treatment for COPD. Expert Opin. Investig. Drugs (2002) 11:965-980.
104. LUISETTI M, STURANI C, SELLA D et al.: MR-889, a neutrophil elastase inhibitor, in patients with chronic obstructive pulmonary disease: a double-blind, randomized, placebo-controlled clinical trial. Eur. Respir. J. (1996) 9:1482-1486.
105. KAPUI Z, VARGA M, URBAN-SZABO K et al.: Biochemical and pharmacological characterization of 2-(9-(2-piperidinoethoxy)-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yloxymethyl) -4-(1-methylethyl)-6-methoxy-1,2-benzisothiazol-3(2H)-one-1,1-dioxide (SSR-69071), a novel, orally active elastase inhibitor. J. Pharmacol. Exp. Ther. (2003) 305:451-459.
106. VARGA M, KAPUI Z, BATORI S et al.: A novel orally active inhibitor of HLE. Eur. J. Med. Chem. (2003) 38:421-425.
107. DOVE A: MMP inhibitors: glimmers of hope amidst clinical failures. Nat. Med. (2002) 8:95.
108. SELMAN M, CISNEROS-LIRA J, GAXIOLA M et al.: Matrix metalloproteinases inhibition attenuates tobacco smoke-induced emphysema in guinea-pigs. Chest (2003) 123:1633-1641.
109. CHAMBON P: A decade of molecular biology of retinoic acid receptors. FASEB J. (1996) 10:940-954.
110. NAGPAL S, ATHANIKAR J, CHANDRARATNA RA: Separation of transactivation AP1 antagonism functions of retinoic acid receptor α. J. Biol. Chem. (1995) 270:923-927.
111. ONG DE, CHYTIL F: Changes in levels of cellular retinol- and retinoic-acid-binding proteins of liver and lung during perinatal development of rat. Proc. Natl. Acad. Sci. USA (1976) 73:3976-3978.
112. MASSARO GD, MASSARO D: Postnatal treatment with retinoic acid increases the number of pulmonary alveoli in rats. Am. J. Physiol. (1996) 270:L305-L310.
113. BENOIT G, ALTUCCI L, FLEXOR M et al.: RAR-independent RXR signaling induces t(15;17) leukemia cell maturation. EMBO J. (1999) 18:7011-7018.
114. BERGER J, WAGNER JA: Physiological and therapeutic roles of peroxisome proliferator-activated receptors. Diabetes Technol. Ther. (2002) 4:163-174.
115. ELDER JT, FISHER GJ, ZHANG QY et al.: Retinoic acid receptor gene expression in human skin. J. Invest. Dermatol. (1991) 96:425-433.
116. REES J: The molecular biology of retinoic acid receptors: orphan from good family seeks home. Br. J. Dermatol. (1992) 126:97-104.
117. FISHER GJ, TALWAR HS, XIAO JH et al.: Immunological identification and functional quantitation of retinoic acid and retinoid X receptor proteins in human skin. J. Biol. Chem. (1994) 269:20629-20635.
118. MASSARO GC, MASSARO D, CHAMBON P: Retinoic acid receptor-α regulates pulmonary alveolus formation in mice after, but not during, perinatal period. Am. J. Physiol. Lung Cell Mol. Physiol. (2003) 284:L431-L433.
119. MASSARO GD, MASSARO D, CHAN WY et al.: Retinoic acid receptor-beta: an endogenous inhibitor of the perinatal formation of pulmonary alveoli. Physiol. Genomics (2000) 4:51-57.
120. MCGOWAN S, JACKSON SK, JENKINS-MOORE M, DAI HH, CHAMBON P, SNYDER JM: Mice bearing deletions of retinoic acid receptors demonstrate reduced lung elastin and alveolar numbers. Am. J. Respir. Cell Mol. Biol. (2000) 23:162-167.
121. NO AUTHORS LISTED: Selective RAR-γ agonists for treating emphysema. Expert Opin. Ther. Patents (2002) 12:1107-1110.
122. GUZMAN K, GRAY TE, YOON JH, NETTESHEIM P: Quantitation of mucin RNA by PCR reveals induction of both MUC2 MUC5AC mRNA levels by retinoids. Am. J. Physiol. (1996) 271:L1023-L1028.
123. YOON JH, GRAY T, GUZMAN K, KOO JS, NETTESHEIM P: Regulation of the secretory phenotype of human airway epithelium by retinoic acid, triiodothyronine, and extracellular matrix. Am. J. Respir. Cell Mol. Biol. (1997) 16:724-731.
124. KOO JS, YOON JH, GRAY T, NORFORD D, JETTEN AM, NETTESHEIM P: Restoration of the mucous phenotype by retinoic acid in retinoid-deficient human bronchial cell cultures: changes in mucin gene expression. Am. J. Respir. Cell Mol. Biol. (1999) 20:43-52.
125. KOO JS, JETTEN AM, BELLONI P, YOON JH, KIM YD, NETTESHEIM P: Role of retinoid receptors in the regulation of mucin gene expression by retinoic acid in human tracheobronchial epithelial cells. Biochem. J. (1999) 338:351-357.
126. APFEL C, BAUER F, CRETTAZ M et al.: A retinoic acid receptor α antagonist selectively counteracts retinoic acid effects. Proc. Natl. Acad. Sci. USA (1992) 89:7129-7133.
127. KOO JS, KIM YD, JETTEN AM, BELLONI P, NETTESHEIM P: Overexpression of mucin genes induced by interleukin-1 β, tumor necrosis factor-α, lipopolysaccharide, and neutrophil elastase is inhibited by a retinoic acid receptor α antagonist. Exp. Lung Res. (2002) 28:315-332.
128. MASSARO GD MASSARO D: Retinoic acid treatment abrogates elastase-induced pulmonary emphysema in rats. Nat. Med. (1997) 3:675-677.
129. BELLONI PN, GARVIN L, MAO CP, BAILEY-HEALY I, LEAFFER D: Effects of all-trans-retinoic acid in promoting alveolar repair. Chest (2000) 117:235S-241S.
130. AN L, ZHANG H, PANG B et al.: [Prophylactic effect of retinoic acid on chronic obstructive pulmonary emphysema in rats]. Zhonghua Jie. He. He. Hu Xi. Za Zhi. (2002) 25:356-359.
131. MESHI B, VITALIS TZ, IONESCU D et al.: Emphysematous lung destruction by cigarette smoke. The effects of latent adenoviral infection on the lung inflammatory response. Am. J. Respir. Cell Mol. Biol. (2002) 26:52-57.
132. MAO JT, GOLDIN JG, DERMAND J et al.: A pilot study of all-trans-retinoic acid for the treatment of human emphysema. Am. J. Respir. Crit. Care Med. (2002) 165:718-723.
133. KRUMME D, WENZEL H, TSCHESCHE H: Hydroxamate derivatives of substrate-analogous peptides containing aminomalonic acid are potent inhibitors of matrix metalloproteinases. FEBS Lett. (1998) 436:209-212.
134. KRUMME D, TSCHESCHE H: Oxal hydroxamic acid derivatives with inhibitory activity against matrix metalloproteinases. Bioorg. Med. Chem. Lett. (2002) 12:933-936.
135. COPELAND RA, LOMBARDO D, GIANNARAS J, DECICCO CP: Estimating Ki values for tight binding inhibitors from dose-response plots. Bioorg. Med. Chem. Lett. (1995) 5:1947-1952.
136. MOHLER KM, SLEATH PR, FITZNER JN et al.: Protection against a lethal dose of endotoxin by an inhibitor of tumour necrosis factor processing. Nature (1994) 370:218-220.
137. 1 integrin from phage display library. J. Biol. Chem. (1993) 268:20205-20210.
138. MAGERT HJ, STANDKER L, KREUTZMANN P et al.: LEKTI, a novel 15-domain type of human serine proteinase inhibitor. J. Biol. Chem. (1999) 274:21499-21502.
139. MAGERT HJ, KREUTZMANN P, DROGEMULLER K et al.: The 15-domain serine proteinase inhibitor LEKTI: biochemical properties, genomic organization, and pathophysiological role. Eur. J. Med. Res. (2002) 7:49-56.
140. MAGERT HJ, KREUTZMANN P, STANDKER L, WALDEN M, DROGEMULLER K, FORSSMANN WG: LEKTI: a multidomain serine proteinase inhibitor with pathophysiological relevance. Int. J. Biochem. Cell Biol. (2002) 34:573-576.
141. DEL MAR EG, LARGMAN C, BRODRICK JW, FASSETT M, GEOKAS MC: Substrate specificity of human pancreatic elastase 2. Biochemistry (1980) 19:468-472.
142. GROUTAS WC, KUANG R, VENKATARAMAN R, EPP JB, RUAN S, PRAKASH O: Structure-based design of a general class of mechanism-based inhibitors of the serine proteinases employing a novel amino acid-derived heterocyclic scaffold. Biochemistry (1997) 36:4739-4750.
143. SCHECHTER NM, JORDAN LM, JAMES AM, COOPERMAN BS, WANG ZM, RUBIN H: Reaction of human chymase with reactive site variants of alpha 1-antichymotrypsin. Modulation of inhibitor versus substrate properties. J. Biol. Chem. (1993) 268:23626-23633.
144. MAUBACH G, SCHILLING K, ROMMERSKIRCH W et al.: The inhibition of cathepsin S by its propeptide-specificity and mechanism of action. Eur. J. Biochem. (1997) 250:745-750.
145. HORVATH ZS, CORTHALS GL, WRIGLEY CW, MARGOLIS J: Multifunctional apparatus for electrokinetic processing of proteins. Electrophoresis (1994) 15:968-971.
146. FEHRENBACH H: Animal models of chronic obstructive pulmonary disease: some critical remarks. Pathobiology (2002) 70:277-283.
147. WRIGHT JL, CHURG A: Animal models of cigarette smoke-induced COPD. Chest (2002) 122:301S-306S.
148. JONES PW, QUIRK FH, BAVEYSTOCK CM: The St George's respiratory questionnaire. Respir. Med. (1991) 85(Suppl.B):25-31.
149. NEWELL JD Jr: CT of emphysema. Radiol. Clin. North Am. (2002) 40:31-42vii.
150. KHARITONOV SA, BARNES PJ: Exhaled markers of pulmonary disease. Am. J. Respir. Crit. Care Med. (2001) 163:1693-1722.