Chronic inflammation in the cystic fibrosis lung: Alterations in inter- and intracellular signaling

Clinical Reviews in Allergy and Immunology

Volumn 34, Issue 2, 2008, Pages 146-162

  Nichols, David ^a   Chmiel, James ^a   Berger, Melvin ^a  

^a CASE WESTERN RESERVE UNIVERSITY   (United States)

Author keywords

Cystic fibrosis; Cytokines; Inflammation; Intra and intercellular communications; Lung

Indexed keywords

CHLORIDE CHANNEL; GAMMA INTERFERON; GUANOSINE TRIPHOSPHATASE; I KAPPA B; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INDUCIBLE NITRIC OXIDE SYNTHASE; INTERFERON REGULATORY FACTOR 1; INTERLEUKIN 1; INTERLEUKIN 10; INTERLEUKIN 17; INTERLEUKIN 1BETA; INTERLEUKIN 23; INTERLEUKIN 23P19; INTERLEUKIN 6; INTERLEUKIN 8; LIPID; MYELOID DIFFERENTIATION FACTOR 88; NITRIC OXIDE; PROTEIN P50; STAT PROTEIN; STAT1 PROTEIN; SYNAPTOTAGMIN I; TOBRAMYCIN; TOLL LIKE RECEPTOR 4; TRANSCRIPTION FACTOR AP 1; TRANSFORMING GROWTH FACTOR BETA; TRANSMEMBRANE CONDUCTANCE REGULATOR; TUMOR NECROSIS FACTOR; TUMOR NECROSIS FACTOR ALPHA; UNINDEXED DRUG; CYTOKINE; I KAPPA B KINASE;

AIRWAY OBSTRUCTION; CHRONIC INFLAMMATION; CILIARY MOTILITY; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DISEASE COURSE; GENE EXPRESSION; GENE MUTATION; HUMAN; IMMUNE RESPONSE; INFECTION; LUNG FIBROSIS; MORBIDITY; MORTALITY; NONHUMAN; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; ANIMAL; CYSTIC FIBROSIS; IMMUNOLOGY; INFLAMMATION; LUNG; METABOLISM; PATHOLOGY;

AIRWAY OBSTRUCTION; ANIMALS; CYSTIC FIBROSIS; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; CYTOKINES; GTP PHOSPHOHYDROLASES; HUMANS; I-KAPPA B KINASE; INFECTION; INFLAMMATION; LUNG; NF-KAPPA B; SIGNAL TRANSDUCTION;

EID: 48649104569     PISSN: 10800549     EISSN: None     Source Type: Journal    
DOI: 10.1007/s12016-007-8039-9     Document Type: Review

References (171)

1. LC Tsui 1995 The cystic fibrosis transmembrane conductance regulator gene Am J Respir Crit Care Med 151 3 Pt 2 S47 S53
2. J Zielenski LC Tsui 1995 Cystic fibrosis: genotypic and phenotypic variations Annu Rev Genet 29 777 807
3. JE Mickle GR Cutting 2000 Genotype-phenotype relationships in cystic fibrosis Med Clin North Am 84 3 597 607
4. M Claustres 2005 Molecular pathology of the CFTR locus in male infertility Reprod Biomed Online 10 1 14 41
5. GR Cutting 2005 Modifier genetics: cystic fibrosis Annu Rev Genomics Hum Genet 6 237 260
6. ML Drumm MW Konstan MD Schluchter Gene Modifier Study Group 2005 Genetic modifiers of lung disease in cystic fibrosis N Engl J Med 353 1443 1453
7. JW Hanrahan MA Wioland 2004 Revisiting cystic fibrosis transmembrane conductance regulator structure and function Proc Am Thorac Soc 1 1 17 21
8. R Greger M Mall M Bleich 1996 Regulation of epithelial ion channels by the cystic fibrosis transmembrane conductance regulator J Mol Med 74 527 534
9. K Kunzelmann R Schreiber R Nitschke M Mall 2000 Control of epithelial Na+ conductance by the cystic fibrosis transmembrane conductance regulator Pflugers Arch 440 193 201
10. Q Jiang J Li R Dubroff YJ Ahn 2000 Epithelial sodium channels regulate cystic fibrosis transmembrane conductance regulator chloride channels in Xenopus oocytes J Biol Chem 275 13266 13274
11. - transport by cystic fibrosis transmembrane conductance regulator (CFTR) contributes to the inhibition of epithelial Na+ channels (ENaCs) in Xenopus oocytes co-expressing CFTR and ENaC J Physiol 508 Pt 3 825 836
12. MJ Stutts BC Rossier RC Boucher 1997 Cystic fibrosis transmembrane conductance regulator inverts protein kinase A-mediated regulation of epithelial sodium channel single channel kinetics J Biol Chem 272 14037 14040
13. E Hummler P Barker J Gatzy 1996 Early death due to defective neonatal lung liquid clearance in alpha-ENaC-deficient mice Nat Genet 12 325 328
14. JM Zahm S Baconnais DJ Davidson 2001 X-ray microanalysis of airway surface liquid collected in cystic fibrosis mice Am J Physiol Lung Cell Mol Physiol 281 L309 L313
15. S Jayaraman NS Joo B Reitz 2001 Submucosal gland secretions in airways from cystic fibrosis patients have normal [Na(+)] and pH but elevated viscosity Proc Natl Acad Sci U S A 98 8119 8123
16. S Jayaraman Y Song L Vetrivel 2001 Noninvasive in vivo fluorescence measurement of airway-surface liquid depth, salt concentration, and pH J Clin Invest 107 317 324
17. H Matsui CW Davis R Tarran RC Boucher 2000 Osmotic water permeabilities of cultured, well-differentiated normal and cystic fibrosis airway epithelia J Clin Invest 105 1419 1427
18. H Matsui BR Grubb R Tarran 1998 Evidence for periciliary liquid layer depletion, not abnormal ion composition, in the pathogenesis of cystic fibrosis airways disease Cell 95 1005 1015
19. M Mall BR Grubb JR Harkema 2004 Increased airway epithelial Na+ absorption produces cystic fibrosis-like lung disease in mice Nat Med 10 487 493
20. PM Quinton 1999 Physiological basis of cystic fibrosis: a historical perspective Physiol Rev 79 1 Suppl S3 S22
21. RC Stern 1997 The diagnosis of cystic fibrosis N Engl J Med 336 7 487 491
22. J Bijman H De Jonge J Wine 1988 Cystic fibrosis advantage Nature 336 6198 430
23. SE Gabriel KN Brigman BH Koller RC Boucher MJ Stutts 1994 Cystic fibrosis heterozygote resistance to cholera toxin in the cystic fibrosis. mouse model Science 266 5182 107 109
24. CW Bedrossian SD Greenberg DB Singer 1976 The lung in cystic fibrosis Hum Pathol 7 195 204
25. J Sturgess J Imrie 1982 Quantitative evaluation of the development of tracheal submucosal glands in infants with cystic fibrosis and control infants Am J Pathol 106 303 311
26. Tomashefski JF, Abramowsky CR, Dahms BB (1993) The pathology of cystic fibrosis. In: Davis PB (ed) Cystic fibrosis. Marcel Dekker, New York, pp 435-489
27. MW Konstan M Berger 1997 Current understanding of the inflammatory process in cystic fibrosis: onset and etiology Pediatr Pulmonol 24 137 142
28. TZ Khan JS Wagener T Bost 1995 Early pulmonary inflammation in infants with cystic fibrosis Am. J Respir Crit Care Med 151 1075 1082
29. DS Armstrong SM Hook KM Jamsen 2005 Lower airway inflammation in infants with cystic fibrosis detected by newborn screening Pediatr Pulmonol 40 500 510
30. P Birrer NG McElvaney A Rudeberg 1994 Protease-antiprotease imbalance in the lungs of children with cystic fibrosis Am J Respir Crit Care Med 150 207 213
31. A Cantin 1995 Cystic fibrosis lung inflammation: early, sustained, and severe Am J Respir Crit Care Med 151 4 939 941
32. E DiMango AJ Ratner R Bryan 1998 Activation of NF-kappaB by adherent Pseudomonas aeruginosa in normal and cystic fibrosis respiratory epithelial cells J Clin Invest 101 11 2598 2605
33. TL Bonfield MW Konstan M Berger 1999 Altered respiratory epithelial cell cytokine production in cystic fibrosis J Allergy Clin Immunol 104 1 72 78
34. M Berger 2002 Lung inflammation early in cystic fibrosis: bugs are indicted, but the defense is guilty Am J Respir Crit Care Med 165 7 857 858
35. K Balough M McCubbin M Weinberger 1995 The relationship between infection and inflammation in the early stages of lung disease from cystic fibrosis Pediatr Pulmonol 20 2 63 70
36. DS Armstrong K Grimwood R Carzino 1995 Lower respiratory infection and inflammation in infants with newly diagnosed cystic fibrosis BMJ 310 6997 1571 1572
37. DS Armstrong K Grimwood JB Carlin 1997 Lower airway inflammation in infants and young children with cystic fibrosis Am J Respir Crit Care Med 156 4 Pt 1 1197 1204
38. JF Chmiel MW Konstan M Berger 2002 The role of inflammation in the pathophysiology of CF lung disease Clin Review Allergy Immunol 23 1 5 27
39. PB Davis M Drumm MW Konstan 1996 State of the art: Cystic fibrosis Am J Resp Crit Care Med 154 1229 1256
40. CF Foundation Patient Registry Annual Data report (2005), CFF, Bethesda, MD, 2006
41. JM Quan HA Tiddens JP Sy Pulmozyme Early Intervention Trial Study Group 2001 A two-year randomized, placebo-controlled trial of dornase alfa in young patients with cystic fibrosis with mild lung function abnormalities J Pediatr 139 813 820
42. K McCoy S Hamilton C Johnson 1996 Effects of 12-week administration of dornase alfa in patients with advanced cystic fibrosis lung disease Chest 110 889 895
43. ME Hodson 1995 Aerosolized dornase alfa (rhDNase) for therapy of cystic fibrosis Am J Respir Crit Care Med 151 S70 S74
44. SH Donaldson WD Bennett KL Zeman 2006 Mucus clearance and lung function in cystic fibrosis with hypertonic saline N Engl J Med 354 241 250
45. MR Elkins M Robinson BR Rose 2006 A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis N Engl J Med 354 229 240
46. A Bauernfeind RM Bertele K Harms 1987 Qualitative and quantitative microbiological analysis of sputa of 102 patients with cystic fibrosis Infection 15 270 277
47. PH Gilligan 1991 Microbiology of airway disease in patients with cystic fibrosis Clin Microbiol Rev 4 35 51
48. RM Donlan JW Costerton 2002 Biofilms: survival mechanisms of clinically relevant microorganisms Clin Microbiol Rev 15 167 193
49. PK Singh AL Schaefer MR Parsek 2000 Quorum-sensing signals indicate that cystic fibrosis lungs are infected with bacterial biofilms Nature 407 762 764
50. JW Costerton J Lam K Lam R Chan 1983 The role of the microcolony mode of growth in the pathogenesis of Pseudomonas aeruginosa infections Rev Infect Dis 5 Suppl 5 S867 S873
51. AB Lang A Rudeberg MH Schoni 2004 Vaccination of cystic fibrosis patients against Psuedomonas aeruginosa reduces the proportion of patients infected and delays time to infection Pediatr Infect Dis J 23 504 510
52. AW Zeurcher MP Horn JU Que 2006 Antibody responses induced by long-term vaccination with an octovalent conjugate Pseudomonas aeruginosa vaccine in children with cystic fibrosis FEMS Immunol Med Microbiol 47 302 308
53. F Festini R Buzzetti C Bassi 2006 Isolation measures for prevention of infection with respiratory pathogens in cystic fibrosis: a systematic review J Hosp Infect 64 1 6
54. L Saiman J Siegel 2004 Infection control in cystic fibrosis Clin Microbiol Rev 17 57 71
55. HR Stutman JM Lieberman E Nussbaum MI Marks 2002 Antibiotic prophylaxis in infants and young children with cystic fibrosis: a randomized controlled trial J Pediatr 140 299 305
56. B Frederiksen C Koch N Hoiby 1997 Antibiotic treatment of initial colonization with Pseudomonas aeruginosa postpones chronic infection and prevents deterioration of pulmonary function in cystic fibrosis Pediatr Pulmonol 23 330 335
57. HG Wiesemann G Steinkamp F Ratjen 1998 Placebo-controlled, double-blind, randomized study of aerosolized tobramycin for early treatment of P. aeruginosa colonization in cystic fibrosis Pediatr Pulmonol 25 88 92
58. NH Valerius C Koch N Hoiby 1991 Prevention of chronic P. aeruginosa colonization in cystic fibrosis by early treatment Lancet 338 725 726
59. RL Gibson JL Burns BW Ramsey 2003 Pathophysiology and management of pulmonary infections in cystic fibrosis Am J Respir Crit Care Med 168 8 918 951
60. Ryan G, Mukhopadhyay S, Singh M (2003) Nebulised anti-psuedomonal antibiotics for cystic fibrosis. Cochrane Database Syst Rev vol. 3. CD001021
61. BW Ramsey MS Pepe JM Quan 1999 Intermittent administration of inhaled tobramycin in patients with cystic fibrosis N Engl J Med 340 23 30
62. M Spino 1991 Pharmacokinetics of drugs in cystic fibrosis Clin Rev Allergy 9 169 210
63. DJ Touw AA Vinks JW Mouton 1998 Pharmacokinetic optimization of antibacterial treatment in patients with cystic fibrosis: current practice and suggestions for future directions Clin Pharacokinet 35 437 459
64. E Rey J Treluyer G Pons 1998 Drug disposition in cystic fibrosis Clin Pharmacokinet 35 313 329
65. CW Bedrossian SD Greenberg DB Singer 1976 The lung in cystic fibrosis. A quantitative study including prevalence of pathologic findings among different age groups Hum Pathol 7 2 195 204
66. M Berger 1991 Inflammation in the lung in cystic fibrosis. A vicious cycle that does more harm than good? Clin Rev Allergy Spring-Summer 9 1-2 119 142
67. TL Bonfield JR Panuska MW Konstan 1995 Inflammatory cytokines in cystic fibrosis lungs Am J Respir Crit Care Med 152 6 Pt 1 2111 2118 [Published erratum appears in Am J Respir Crit Care Med 1996 Oct;154(4 Pt 1):1217]
68. KK Kirchner JS Wagener TZ Khan 1996 Increased DNA levels in bronchoalveolar lavage fluid obtained from infants with cystic fibrosis Am J Respir Crit Care Med 154 5 1426 1429
69. MW Konstan KA Hilliard TM Norvell 1994 Bronchoalveolar lavage findings in cystic fibrosis patients with stable, clinically mild lung disease suggest ongoing infection and inflammation Am J Respir Crit Care Med 150 2 448 454 [published erratum appears in Am J Respir Crit Care Med 1995 Jan:151(1)260]
70. MW Konstan RW Walenga KA Hilliard 1993 Leukotriene B4 is markedly elevated in the epithelial lining fluid of patients with cystic fibrosis Am Rev Respir Dis 148 4 Pt 1 896 901
71. TL Noah HR Black PW Cheng 1997 Nasal and bronchoalveolar lavage fluid cytokines in early cystic fibrosis J Infect Dis 175 3 638 647
72. MS Muhlebach PW Stewart MW Leigh 1999 Quantitation of inflammatory response to bacteria in young cystic fibrosis and control patients Am J Respir Crit Care Med 160 1 186 191
73. MS Muhlebach TL Noah 2002 Endotoxin activity and inflammatory markers in the airways of young patients with cystic fibrosis Am J Respir Crit Care Med 165 7 911 915
74. V Starosta E Rietschel K Paul 2006 Oxidative changes of bronchoalveolar proteins in cystic fibrosis Chest 129 431 437
75. J Hull P Vervaart K Grimwood P Phelan 1997 Pulmonary oxidative stress response in young children with cystic fibrosis Thorax 52 557 560
76. AJ Kettle T Chan I Osberg 2004 Myeloperoxidase and protein oxidation in the airways of young children with cystic fibrosis Am J Respir Crit Care Med 170 1317 1323
77. JA Nadel 1991 Role of enzymes from inflammatory cells on airway submucosal gland secretion Respiration 58 Suppl 1 3 5
78. RA Caldwell RC Boucher MJ Stutts 2005 Neutrophil elastase activates near-silent epithelial Na+ channels and increases airway epithelial Na+ transport Am J Physiol Lung Cell Mol Physiol 288 5 L813 L819
79. MF Tosi H Zakem M Berger 1990 Neutrophil elastase cleaves C3bi on opsonized pseudomonas as well as CR1 on neutrophils to create a functionally important opsonin receptor mismatch J Clin Invest 86 1 300 308
80. RW Vandivier VA Fadok PR Hoffmann 2002 Elastase-mediated phosphatidylserine receptor cleavage impairs apoptotic cell clearance in cystic fibrosis and bronchiectasis J Clin Invest 109 5 661 670
81. JF Chmiel MW Konstan 2005 Anti-inflammatory medications for cystic fibrosis lung disease: selecting the most appropriate agent Treat Respir Med 4 255 273
82. PM Henson 1991 Resolution of inflammation A perspective. Chest 99 3 Suppl 2S 6S
83. TL Bonfield MW Konstan P Burfeind 1995 Normal bronchial epithelial cells constitutively produce the anti-inflammatory cytokine interleukin-10, which is downregulated in cystic fibrosis Am J Respir Cell Mol Biol 13 3 257 261
84. E Osika JM Cavaillon K Chadelat 1999 Distinct sputum cytokine profiles in cystic fibrosis and other chronic inflammatory airway disease Eur Respir J 14 2 339 346
85. IM Balfour-Lynn A Laverty R Dinwiddie 1996 Reduced upper airway nitric oxide in cystic fibrosis Arch Dis Child 75 4 319 322
86. H Grasemann E Michler M Wallot F Ratjen 1997 Decreased concentration of exhaled nitric oxide (NO) in patients with cystic fibrosis Pediatr Pulmonol 24 3 173 177
87. CJ Chelen Y Fang GJ Freeman 1995 Human alveolar macrophages present antigen ineffectively due to defective expression of B7 costimulatory cell surface molecules J Clin Invest 95 3 1415 1421
88. J Soltys T Bonfield J Chmiel M Berger 2002 Functional IL-10 deficiency in the lung of cystic fibrosis (cftr-/-) and IL-10 knockout mice causes increased expression and function of B7 costimulatory molecules on alveolar macrophages J Immunol 168 4 1903 1910
89. + T lymphocytes expressing mutant cystic fibrosis transmembrane conductance regulator (CFTR) Clin Exp Immunol 106 2 374 388
90. G Cox 1996 IL-10 enhances resolution of pulmonary inflammation in vivo by promoting apoptosis of neutrophils Am J Physiol 271 4 Pt 1 L566 L571
91. NN Khodarev IA Sokolova AT Vaughan 1998 Mechanisms of induction of apoptotic DNA fragmentation Int J Radiat Biol 73 5 455 467
92. AB Lentsch TP Shanley V Sarma PA Ward 1997 In vivo suppression of NF-κB and preservation of IκBα by interleukin-10 and interleukin-13 J Clin Invest 100 10 2443 2448
93. AJG Schottelius MW Mayo RB Sartor AS Baldwin Jr 1999 Interleukin-10 signaling blocks inhibitor of κB kinase activity and nuclear factor κB DNA binding J Biol Chem 274 45 31868 31874
94. TA Hamilton Y Ohmori J Tebo 2002 Regulation of chemokine expression by antiinflammatory cytokines Immunol Res 25 3 229 245
95. ID Welters C Fimiani TV Bilfinger GB Stefano 2000 NF-kappaB, nitric oxide and opiate signaling Med Hypotheses 54 2 263 268
96. A Saadane J Soltys M Berger 2005 Role of IL-10 deficiency in excessive nuclear factor-kappaB activation and lung inflammation in cystic fibrosis transmembrane conductance regulator knockout mice J Allergy Clin Immunol 115 2 405 411
97. JF Chmiel MW Konstan A Saadane 2002 Prolonged inflammatory response to acute pseudomonas challenge in IL-10 knockout mice Am J Respir Crit Care Med 165 8 1176 1181
98. A Saadane J Soltys M Berger 2006 Acute Pseudomonas challenge in cystic fibrosis mice causes prolonged nuclear factor-kappa B activation, cytokine secretion, and persistent lung inflammation J Allergy Clin Immunol 117 5 1163 1169
99. JF Chmiel MW Konstan M Berger 2002 Murine models of CF airway infection and inflammation Methods Mol Med 70 495 515
100. A van Heeckeren R Walenga MW Konstan 1997 Excessive inflammatory response of cystic fibrosis mice to bronchopulmonary infection with Pseudomonas aeruginosa J Clin Invest 100 11 2810 2815
101. MW Konstan KM Vargo PB Davis 1992 Ibuprofen attenuates the inflammatory response Pseudomonas aeruginosa in a rat model of chronic pulmonary infection Implications for anti-inflammatory therapy in cystic fibrosis. Am Rev Resp Dis 141 186 192
102. MW Konstan PJ Byard CL Hoppel PB Davis 1995 Effect of high-dose ibuprofen in patients with cystic fibrosis N Engl J Med 332 848 854
103. JF Chmiel MW Konstan JE Knesebeck 1999 IL-10 attenuates excessive inflammation in chronic pseudomonas infection in mice Am J Respir Crit Care Med 160 6 2040 2047
104. S Garantziotis DM Brass J Savov 2006 Leukocyte-derived IL-10 reduces subepithelial fibrosis associated with chronically inhaled endotoxin Am J Respir Cell Mol Biol 35 6 662 667
105. PJ Dubin JK Kolls 2007 IL-23 mediates inflammatory responses to mucoid Pseudomonas aeruginosa lung infection in mice Am J Physiol Lung Cell Mol Physiol 292 2 L519 L528
106. DP Hsu A van Heeckeren M Schlucter 2006 IL-17 targeted antibody treatment increases the excessive pulmonary inflammation in CF mice Pediatr Pulmonol Suppl 29 256
107. H Tilg E Trehu MB Atkins 1994 Interleukin-6 (IL-6) as an anti-inflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55 Blood 83 1 113 118
108. M Jordan IG Otterness R Ng 1995 Neutralization of endogenous IL-6 I suppresses induction of IL-1 receptor antagonist J Immunol 154 8 4081 4090
109. R Schindler J Mancilla S Endres R Ghorbani SC Clark CA Dinarello 1990 Correlations and interactions in the production of interleukin-6 (IL-6), IL-1, and tumor necrosis factor (TNF) in human blood mononuclear cells: IL-6 suppresses IL-1 and TNF Blood 75 1 40 47
110. TR Ulich S Yin K Guo 1991 Intratracheal injection of endotoxin and cytokines. II. Interleukin-6 and transforming growth factor beta inhibit acute inflammation Am J Pathol 138 5 1097 1101
111. BE Barton J Shortall JV Jackson 1996 Interleukins 6 and 11 protect mice from mortality in a staphylococcal enterotoxin-induced toxic shock model Infect Immun 64 3 714 718
112. Z Xing J Gauldie G Cox H Baumann 1998 IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses J Clin Invest 101 2 311 320
113. PC Heinrich I Behrmann S Haan 2003 Principles of interleukin (IL)-6-type cytokine signalling and its regulation Biochem J 374 Pt 1 1 20
114. CL Karp LM Flick KW Park S Softic TM Greer R Keledjia 2004 Defective lipoxin-mediated anti-inflammatory activity in the cystic fibrosis airway Nat Immunol 5 4 388 392
115. SD Freedman JC Shea PG Blanco JG Alvarez 2000 Fatty acids in cystic fibrosis Curr Opin Pulm Med 6 6 530 532
116. SD Freedman D Weinstein PG Blanco 2002 Characterization of LPS-induced lung inflammation in cftr-/- mice and the effect of docosahexaenoic acid J Appl Physiol 92 5 2169 2176
117. HL Elmer KG Brady ML Drumm TJ Kelley 1999 Nitric oxide-mediated regulation of transepithelial sodium and chloride transport in murine nasal epithelium Am J Physiol 276 3 Pt 1 L466 L473
118. SA Kharitonov PJ Barnes 2001 Exhaled markers of pulmonary disease. State of the art Am J Respir Crit Care Med 163 7 1693 1722
119. MJ Mhanna T Ferkol RJ Martin 2001 Nitric oxide deficiency contributes to impairment of airway relaxation in cystic fibrosis mice Am J Respir Cell Mol Biol 24 5 621 626
120. AW Smith J Green CE Eden ML Watson 1999 Nitric oxide-induced potentiation of the killing of Burkholderia cepacia by reactive oxygen species: implications for cystic fibrosis J Med Microbiol 48 5 419 423
121. S Zheng W Xu S Bose AK Banerjee SJ Haque SC Erzurum 2004 Impaired nitric oxide synthase-2 signaling pathway in cystic fibrosis airway epithelium Am J Physiol Lung Cell Mol Physiol 287 2 L374 L381
122. TJ Kelley ML Drumm 1998 Inducible nitric oxide synthase expression is reduced in cystic fibrosis murine and human airway epithelial cells J Clin Invest 102 6 1200 1207
123. WK Steagall HL Elmer KG Brady TJ Kelley 2000 Cystic fibrosis transmembrane conductance regulator-dependent regulation of epithelial inducible nitric oxide synthase expression Am J Respir Cell Mol Biol 22 1 45 50
124. QH Meng DR Springall AE Bishop 1998 Lack of inducible nitric oxide synthase in bronchial epithelium: a possible mechanism of susceptibility to infection in cystic fibrosis J Pathol 184 3 323 331
125. S Zheng S Erzurum 2001 Regulation of epithelial reactive oxygen and nitrogen species by inflammatory stimuli Pediatr Pulmonol Suppl 12 128 129
126. S Zheng BP De S Choudhary SA Comhair T Goggans R Slee 2003 Impaired innate host defense causes susceptibility to respiratory virus infections in cystic fibrosis Immunity 18 5 619 630
127. W Xu S Zheng TM Goggans 2006 Cystic fibrosis and normal human airway epithelial cell response to influenza A viral infection J Interferon Cytokine Res 26 9 609 627
128. D Kube U Sontich D Fletcher PB Davis 2001 Proinflammatory cytokine responses to P. aeruginosa infection in human airway epithelial cell lines Am J Physiol Lung Cell Mol Physiol 280 3 L493 L502
129. R Bryan D Kube A Perez P Davis A Prince 1998 Overproduction of the CFTR R domain leads to increased levels of asialoGM1 and increased Pseudomonas aeruginosa binding by epithelial cells Am J Respir Cell Mol Biol 19 2 269 277
130. A Perez AC Issler CU Cotton 2006 CFTR inhibition mimics the cystic fibrosis inflammatory profile J Physiol Lung Cell Mol Physiol 292 L383 L395
131. TE Machen 2006 Innate immune response in CF airway epithelia: hyperinflammatory? Am J Physiol Cell Physiol 291 2 C218 C230
132. CM Ribeiro AM Paradiso MA Carew 2005 Cystic fibrosis airway epithelial Ca2+ i signaling: the mechanism for the larger agonist-mediated Ca2+ i signals in human cystic fibrosis airway epithelia J Biol Chem 280 11 10202 10209
133. AJ Ratner R Bryan A Weber 2001 Cystic fibrosis pathogens activate Ca2+ -dependent mitogen-activated protein kinase signaling pathways in airway epithelial cells J Biol Chem 276 22 19267 19275
134. O Tabary E Boncoeur R de Martin 2006 Calcium-dependent regulation of NF-(kappa)B activation in cystic fibrosis airway epithelial cells Cell Signal 18 5 652 660
135. TV McDonald PT Nghiem P Gardner CL Martens 1992 Human lymphocytes transcribe the cystic fibrosis transmembrane conductance regulator gene and exhibit CF-defective cAMP-regulated chloride current J Biol Chem 267 5 3242 3248
136. D Oceandy BJ McMorran SN Smith 2002 Gene complementation of airway epithelium in the cystic fibrosis mouse is necessary and sufficient to correct the pathogen clearance and inflammatory abnormalities Hum Mol Genet 11 9 1059 1067
137. AM van Heeckeren PB Davis 2004 Examining the contribution of resident and migratory cells in mediating the exaggerated inflammatory response in cystic fibrosis lung infections with mucoid P. aeruginosa Pediatric Pulmonology Suppl. 27 274
138. F Xu A Krause J Joh 2006 Suppression of CFTR expression in alveolar macrophages enhances proinflamatory response to P. aeruginosa Pediatr Pulmon Suppl 29 253
139. M Karin Y Ben-Neriah 2000 Phosphorylation meets ubiquitination: The control of NF-κB activity Ann Rev Immunol 18 621 663
140. PJ Barnes M Karin 1997 NF-κB: A pivotal transcription factor in chronic inflammatory diseases N Engl J Med 336 1066 1071
141. C Scheidereit 2006 IkappaB kinase complexes: gateways to NF-kappaB activation and transcription Oncogene 25 51 6685 6705
142. A Hoffmann A Levchenko ML Scott D Baltimore 2002 The IκB-NF- κB signaling module: temporal control and selective gene activation Science 298 1241 1245
143. FH Guo HR De Raeve TW Rice 1995 Continuous nitric oxide synthesis by inducible nitric oxide synthase in normal human airway epithelium in vivo Proc Natl Acad Sci U S A 92 17 7809 7813
144. TJ Kelley HL Elmer 2000 In vivo alterations of IFN regulatory factor-1 and PIAS1 protein levels in cystic fibrosis epithelium J Clin Invest 106 3 403 410
145. NC Kraynack DA Corey HL Elmer TJ Kelley 2002 Mechanisms of NOS2 regulation by Rho GTPase signaling in airway epithelial cells Am J Physiol Lung Cell Mol Physiol 283 3 L604 L611
146. NE Kreiselmeier NC Kraynack DA Corey TJ Kelley 2003 Statin-mediated correction of STAT1 signaling and inducible nitric oxide synthase expression in cystic fibrosis epithelial cells Am J Physiol Lung Cell Mol Physiol 285 6 L1286 L1295
147. JY Lee HL Elmer KR Ross TJ Kelley 2004 Isoprenoid-mediated control of SMAD3 expression in a cultured model of cystic fibrosis epithelial cells Am J Respir Cell Mol Biol 31 2 234 240
148. I Zelvyte R Dominaitiene M Crisby S Janciauskiene 2002 Modulation of inflammatory mediators and PPARgamma and NFkappaB expression by pravastatin in response to lipoproteins in human monocytes in vitro Pharmacol Res 45 2 147 154
149. G Martin H Duez C Blanquart 2001 Statin-induced inhibition of the Rho-signaling pathway activates PPARalpha and induces HDL apoA-I J Clin Invest 107 11 1423 1432
150. M Ollero O Junaidi MM Zaman 2004 Decreased expression of peroxisome proliferators activated receptor gamma in cftr -/- mice J Cell Physiol 200 2 235 244
151. S Green 1995 PPAR: A mediator of peroxisome proliferators action Mutat Res 333 1-2 101 109
152. W Vanden Berghe L Vermeulen P Delerive 2003 A paradigm for gene regulation: inflammation, NF-kappaB, and PPAR Adv Exp Med Biol 544 181 196
153. V Reynders S Loitsch C Steinhauer 2006 Peroxisome proliferator-activated receptor alpha (PPAR alpha) down-regulation in cystic fibrosis lymphocytes Respir Res 7 104
154. PB Davis S Gupta J Eastman MW Konstan 2003 Inhibition of proinflammatory cytokine production by PPARgamma agonists in airway epithelial cells Pediatr Pulmonol Suppl 25 A246
155. AM van Heeckeren PB Davis 2004 Effects of pioglitazone treatment in cystic fibrosis and wild type mice infected with Pseudomonas aeruginosa Pediatric Pulmonology Suppl 28 237
156. MW Konstan PB Davis 2002 Pharmacological approaches for the discovery and development of new anti-inflammatory agents for the treatment of cystic fibrosis Adv Drug Deliv Rev 54 1409 1423
157. N Auphan A DiDonato C Rosette A Helmberg M Karin 1995 Immunosuppression by glucocorticoids: Inhibition of NF-κB activity through induction of IκB synthesis Science 270 286 290
158. MJ Yin Y Yamato RB Gaynor 1998 The anti-inflammatory agents aspirin and salicylate inhibit the activity of IκB kinase-β Nature 396 77 80
159. HS Auerbach M Williams JA Kirkpatrick HR Colten 1985 Alternate-day prednisone reduces morbidity and improves pulmonary function in cystic fibrosis Lancet 2 686 688
160. H Eigen BJ Rosenstein S FitzSimmons DV Schidlow 1995 A multicenter study of alternate-day prednisone therapy to patients with cystic fibrosis. Cystic Fibrosis Foundation Prednisone Trial Group J Pediatr 126 515 523
161. HC Lai SC FitzSimmons DB Allen 2000 Risk of persistent growth impairment after alternate-day prednisone treatment in children with cystic fibrosis N Engl J Med 342 12 851 859
162. CM Oermann MM Sockrider MW Konstan 1999 The use of anti-inflammatory medications in cystic fibrosis Chest 115 1053 1058
163. N Keicho S Kudoh 2002 Diffuse panbronchiolitis: role of macrolides in therapy Am J Respir Med 1 2 119 131
164. S Abe H Nakamura S Inoue 2000 Interleukin-8 gene repression by clarithromycin is mediated by the activator protein-1 binding site in human bronchial epithelial cells Am J Respir Cell Mol Biol 22 1 51 60
165. T Yamada S Fujieda S Mori 2000 Macrolide treatment decreased the size of nasal polyps and IL-8 levels in nasal avage Am J Rhinol 14 3 143 148
166. C Cigana E Nicolis M Pasetto BM Assael P Melotti 2006 Anti-inflammatory effects of azithromycin in cystic fibrosis airway epithelial cells Biochem Biophys Res Commun 350 4 977 982
167. AC Equi JC Davies H Painter 2006 Exploring the mechanisms of macrolides in cystic fibrosis Respir Med 100 4 687 697
168. L Saiman BC Marshall N Mayer-Hamblett Macrolide Study Group 2003 Azithromycin in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa: a randomized controlled trial JAMA 290 13 1749 1756
169. L Saiman 2004 The use of macrolide antibiotics in patients with cystic fibrosis Curr Opin Pulm Med 10 6 515 523
170. SJ Phaff HA Tiddens HA Verbrugh A Ott 2006 Macrolide resistance of Staphylococcus aureus and Haemophilus species associated with long-term azithromycin use in cystic fibrosis J Antimicrob Chemother 57 4 741 746
171. GA Tramper-Stranders TF Wolfs A Fleer 2007 Maintenance azithromycin treatment in pediatric patients with cystic fibrosis: long-term outcomes related to macrolide resistance and pulmonary function Pediatr Infect Dis J 26 1 8 12