Therapeutic approaches to repair defects in ΔF508 CFTR folding and cellular targeting

Advanced Drug Delivery Reviews

Volumn 54, Issue 11, 2002, Pages 1395-1408

  Powell, Kristina ^a   Zeitlin, Pamela L ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Butyrates; Cystic fibrosis; Endoplasmic reticulum; Golgi apparatus; Ion channel; Isoflavones; Phosphodiesterase inhibitors; Protein chaperone; Xanthines

Indexed keywords

GENES; PROTEINS;

REPAIR DEFECTS;

BIOLOGICAL MEMBRANES;

APIGENIN; CHAPERONE; F508 PROTEIN; GENISTEIN; ION CHANNEL; ISOBUTYLMETHYLXANTHINE; ISOFLAVONE DERIVATIVE; KAEMPFEROL; MUTANT PROTEIN; PHOSPHODIESTERASE INHIBITOR; QUERCETIN; TRANSMEMBRANE CONDUCTANCE REGULATOR; UNCLASSIFIED DRUG; XANTHINE DERIVATIVE;

CHLORIDE CONDUCTANCE; CYSTIC FIBROSIS; DRUG TARGETING; ENDOPLASMIC RETICULUM; HUMAN; MUTATION; NUCLEOTIDE TRANSPORT; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN FOLDING; PROTEIN FUNCTION; PROTEIN STABILITY; REVIEW; RNA TRANSLATION; TEMPERATURE SENSITIVITY;

EID: 0037027950     PISSN: 0169409X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0169-409X(02)00148-5     Document Type: Article

References (95)

1. Mickle J.E., Cutting G.R. Clinical implications of cystic fibrosis transmembrane conductance regulator mutations. Clin. Chest Med. 19:1998;443-458.
2. Anderson M.P., Gregory R.J., Thompson S., Souza D.W. S.Pa, Paul S., Mulligan R.C., Smith A.E., Welsh M.J. Demonstration that CFTR is a chloride channel by alteration of its anion selectivity. Science. 253:1991;202-205.
3. Egan M.E., Schweibert E.M., Guggino W.B. Differential expression of ORCC and CFTR induced by low temperature in CF airway epithelial cells. Am. J. Physiol. (Cell Physiol). 268:(37):1995;C243-C251.
4. Gabriel S.E., Clarke L.L., Boucher R.C., Stutts M.J. CFTR and outward rectifying chloride channels are distinct proteins with a regulatory relationship. Nature. 363:1993;263-268.
5. Stutts M.J., Canessa C.M., Olsen J.C., Hamrick M., Cohn J.A., Rossier B.C., Boucher R.C. CFTR as a cAMP-dependent regulator of sodium channels. Science. 269:1995;847-850.
6. Rosenstein B.J., Cutting G.R. Diagnosis of cystic fibrosis: a consensus statement. J. Pediatr. 132:1998;589-595.
7. Ward C.L., Omura S., Kopito R.R. Degradation of CFTR by the ubiquitin-proteasome pathway. Cell. 83:1995;121-127.
8. Cheng S.H., Gregory R.J., Marshall J., Paul S., Souza D.W., White G.A., O'Riordan C.R., Smith A.E. Defective intracellular transport and processing of CFTR is the molecular basis of most cystic fibrosis. Cell. 63:1990;827-834.
9. Ward C.L., Kopito R.R. Intracellular turnover of cystic fibrosis transmembrane conductance regulator. Inefficient processing and rapid degradation of wild-type and mutant proteins. J. Biol. Chem. 269:1994;25710-25718.
10. Kalin N., Claass A., Sommer M., Puchelle E., Tummler B. ΔF508 CFTR protein expression in tissues from patients with cystic fibrosis. J. Clin. Invest. 103:1999;1379-1389.
11. Dalemans W., Barbry P., Champigny G., Jallat S., Dott K., Dreyer D., Crystal R.G., Pavirani A., Lecocq J.P., Lazdunski M. Altered chloride ion channel kinetics associated with the ΔF508 cystic fibrosis mutation [see comments]. Nature. 354:1991;526-528.
12. Tsui L.C., Buchwald M., Barker D., Braman J.C., Knowlton R., Schumm J.W., Eiberg H., Mohr J., Kennedy D., Plavsic N. Cystic fibrosis locus defined by a genetically linked polymorphic DNA marker. Science. 230:1985;1054-1057.
13. Knowlton R.G., Cohen-Haguenauer O., Van Cong N., Frezal J., Brown V.A., Barker D., Braman J.C., Schumm J.W., Tsui L.C., Buchwald M. A polymorphic DNA marker linked to cystic fibrosis is located on chromosome 7. Nature. 318:1985;380-382.
14. Rommens J.M., Iannuzzi M.C., Kerem B., Drumm M.L., Melmer G., Dean M., Rozmahel R., Cole J.L., Kennedy D., Hidaka N., et al. Identification of the cystic fibrosis gene: Chromosome walking and jumping. Science. 245:1989;1059-1065.
15. Riordan J.R., Rommens J.M., Kerem B., Alon N., Rozmahel R., Grzelczak Z., Zielenski J., Lok S., Plavsic N., Chou J.L., et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA [published erratum appears in Science 1989 Sep. 29;245(4925):1437]. Science. 245: 1989;1066-1073.
16. Jiang Q., Engelhardt J.F. Cellular heterogeneity of CFTR expression and function in the lung: implications for gene therapy of cystic fibrosis. Eur. J. Hum. Genet. 6:1998;12-31.
17. Wang X., Zhang Y., Amberson A., Engelhardt J.F. New models of the tracheal airway define the glandular contribution to airway surface fluid and electrolyte composition. Am. J. Respir. Cell Mol. Biol. 24:2001;195-202.
18. Schwiebert E.M., Egan M.E., Hwang T.H., Fulmer S.B., Allen S.S., Cutting G.R., Guggino W.B. CFTR regulates outwardly rectifying chloride channels through an autocrine mechanism involving ATP. Cell. 81:1995;1063-1073.
19. - channels by protein kinase A corrected by insertion of CFTR [see comments]. Nature. 358:1992;581-584.
20. Ismailov I.I., Awayda M.S., Jovov B., Berdiev B.K., Fuller C.M., Dedman J.R., Kaetzel M., Benos D.J. Regulation of epithelial sodium channels by the cystic fibrosis transmembrane conductance regulator. J. Biol. Chem. 271:1996;4725-4732.
21. Stutts M.J., Canessa C.M., Olsen J.C., Hamrick M., Cohn J.A., Rossier B.C., Boucher R.C. CFTR as a cAMP-dependent regulator of sodium channels. Science. 269:1995;847-850.
22. Yoshimura K., Nakamura H., Trapnell B.C., Dalemans W., Pavirani A., Lecocq J.P., Crystal R.G. The cystic fibrosis gene has a 'housekeeping'-type promoter and is expressed at low levels in cells of epithelial origin. J. Biol. Chem. 266:1991;9140-9144.
23. Bannykh S.I., Bannykh G.I., Fish K.N., Moyer B.D., Riordan J.R., Balch W.E. Traffic pattern of cystic fibrosis transmembrane regulator through the early exocytic pathway. Traffic. 1:2000;852-870.
24. Gilbert A., Jadot M., Leontieva E., Wattiaux-De Coninck S., Wattiaux R. ΔF508 CFTR localizes in the endoplasmic reticulum-Golgi intermediate compartment in cystic fibrosis cells. Exp. Cell Res. 242:1998;144-152.
25. Chang X.B., Cui L., Hou Y.X., Jensen T.J., Aleksandrov A.A., Mengos A., Riordan J.R. Removal of multiple arginine-framed trafficking signals overcomes misprocessing of ΔF508 CFTR present in most patients with cystic fibrosis. Mol. Cell. 4:1999;137-142.
26. Sato S., Ward C.L., Kopito R.R. Cotranslational ubiquitination of cystic fibrosis transmembrane conductance regulator in vitro. J. Biol. Chem. 273:1998;7189-7192.
27. Haws C.M., Nepomuceno I.B., Krouse M.E., Wakelee H., Law T., Xia Y., Nguyen H., Wine J.J. ΔF508-CFTR channels: kinetics, activation by forskolin, and potentiation by xanthines. Am. J. Physiol. 270:1996;C1544-C1555.
28. Schultz B.D., Frizzell R.A., Bridges R.J. Rescue of dysfunctional ΔF508-CFTR chloride channel activity by IBMX. J. Membr. Biol. 170:1999;51-66.
29. Johnson L.G., Olsen J.C., Sarkadi B., Moore K.L., Swanstrom R., Boucher R.C. Efficiency of gene transfer for restoration of normal airway epithelial function in cystic fibrosis. Nat. Genet. 2:1992;21-25.
30. Welsh M.J., Smith A.E. Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis. Cell. 73:1993;1251-1254.
31. Ljunggren H.G., Stam N.J., Ohlen C., Neefjes J.J., Hoglund P., Heemels M.T., Bastin J., Schumacher T.N., Townsend A., Karre K. Empty MHC class I molecules come out in the cold. Nature. 346:1990;476-480.
32. Drumm M.L., Wilkinson D.J., Smit L.S., Worrell R.T., Strong T.V., Frizzell R.A., Dawson D.C., Collins F.S. Chloride conductance expressed by ΔF508 and other mutant CFTRs in Xenopus oocytes. Science. 254:1991;1797-1799.
33. Bear C.E., Li C.H., Kartner N., Bridges R.J., Jensen T.J., Ramjeesingh M., Riordan J.R. Purification and functional reconstitution of the cystic fibrosis transmembrane conductance regulator (CFTR). Cell. 68:1992;809-818.
34. Denning G.M., Anderson M.P., Amara J.F., Marshall J., Smith A.E., Welsh M.J. Processing of mutant cystic fibrosis transmembrane conductance regulator is temperature-sensitive [see comments]. Nature. 358:1992;761-764.
35. Gregory R.J., Rich D.P., Cheng S.H., Souza D.W., Paul S., Manavalan P., Anderson M.P., Welsh M.J., Smith A.E. Maturation and function of cystic fibrosis transmembrane conductance regulator variants bearing mutations in putative nucleotide-binding domains 1 and 2. Mol. Cell Biol. 11:1991;3886-3893.
36. Gekko K., Timasheff S.N. Mechanism of protein stabilization by glycerol: preferential hydration in glycerol-water mixtures. Biochemistry. 20:1981;4667-4676.
37. Shelanski M.L., Gaskin F., Cantor C.R. Microtubule assembly in the absence of added nucleotides. Proc. Natl. Acad. Sci. USA. 70:1973;765-768.
38. Sato S., Ward C.L., Krouse M.E., Wine J.J., Kopito R.R. Glycerol reverses the misfolding phenotype of the most common cystic fibrosis mutation. J. Biol. Chem. 271:1996;635-638.
39. Wang X., Leung S., Guggino S.E. Organic solutes repair the processing defect of the dF508 cystic fibrosis transmembrane conductance regulator protein. Pediatr. Pulmonol. E19:1999;169.
40. Hartl F.U. Molecular chaperones in cellular protein folding. Nature. 381:1996;571-579.
41. Strickland E., Qu B.H., Millen L., Thomas P.J. The molecular chaperone hsc70 assists the in vitro folding of the N-terminal nucleotide-binding domain of the cystic fibrosis transmembrane conductance regulator [in process citation]. J. Biol. Chem. 272:1997;25421-25424.
42. Yang Y., Janich S., Cohn J.A., Wilson J.M. The common variant of cystic fibrosis transmembrane conductance regulator is recognized by hsp70 and degraded in a pre-Golgi nonlysosomal compartment. Proc. Natl. Acad. Sci. USA. 90:1993;9480-9484.
43. Fuller W., Cuthbert A.W. Post-translational disruption of the ΔF508 cystic fibrosis transmembrane conductance regulator (CFTR) - molecular chaperone complex with geldanamycin stabilizes ΔF508 CFTR in the rabbit reticulocyte lysate. J. Biol. Chem. 275:2000;37462-37468.
44. Pind S., Riordan J.R., Williams D.B. Participation of the endoplasmic reticulum chaperone calnexin (p88, IP90) in the biogenesis of the cystic fibrosis transmembrane conductance regulator. J. Biol. Chem. 269:1994;12784-12788.
45. Yang Y., Janich S., Cohn J.A., Wilson J.M. The common variant of cystic fibrosis transmembrane conductance regulator is recognized by hsp70 and degraded in a pre-Golgi nonlysosomal compartment. Proc. Natl. Acad. Sci. USA. 90:1993;9480-9484.
46. Rubenstein R.C., Zeitlin P.L. Sodium 4-phenylbutyrate downregulates Hsc70: implications for intracellular trafficking of ΔF508-CFTR. Am. J. Physiol Cell Physiol. 278:2000;C259-C267.
47. Rubenstein R.C., Lyons B.M. Sodium 4-phenylbutyrate downregulates HSC70 expression by facilitating mRNA degradation. Am. J. Physiol. Lung Cell Mol. Physiol. 281:2001;L43-L51.
48. Choo-Kang L.R., Zeitlin P.L. Induction of HSP70 promotes ΔF508 CFTR trafficking. Am. J. Physiol. Lung Cell Mol. Physiol. 281:2001;L58-L68.
49. Jiang C., Fang S.L., Xiao Y.F., O'Connor S.P., Nadler S.G., Lee D.W., Jefferson D.M., Kaplan J.M., Smith A.E., Cheng S.H. Partial restoration of cAMP-stimulated CFTR chloride channel activity in ΔF508 cells by deoxyspergualin. Am. J. Physiol. 275:1998;C171-C178.
50. Loo M.A., Jensen T.J., Cui L., Hou Y., Chang X.B., Riordan J.R. Perturbation of Hsp90 interaction with nascent CFTR prevents its maturation and accelerates its degradation by the proteasome. EMBO J. 17:1998;6879-6887.
51. Cuisset L., Tichonicky L., Jaffray P., Delpech M. The effects of sodium butyrate on transcription are mediated through activation of a protein phosphatase. J. Biol. Chem. 272:1997;24148-24153.
52. D'Anna J.A., Tobey R.A., Gurley L.R. Concentration-dependent effects of sodium butyrate in Chinese hamster cells: cell-cycle progression, inner-histone acetylation, histone H1 dephosphorylation, and induction of an H1-like protein. Biochemistry. 19:1980;2656-2671.
53. Klehr D., Schlake T., Maass K., Bode J. Scaffold-attached regions (SAR elements) mediate transcriptional effects due to butyrate. Biochemistry. 31:1992;3222-3229.
54. Dover G.J., Brusilow S.W., Samid D. Increased fetal hemoglobin in patients receiving sodium 4-phenylbutyrate. New Engl. J. Med. 327:1992;569-570.
55. Dover G.J., Brusilow S.W., Charache S. Induction of fetal hemoglobin production in subjects with sickle cell anemia by oral sodium phenylbutyrate. Blood. 84:1994;339-343.
56. Collins A.F., Pearson H.A., Giardina P., McDonagh K.T., Brusilow S.W., Dover G.J. Oral sodium phenylbutyrate therapy in homozygous β-thalassemia: a clinical trial. Blood. 85:1995;43-49.
57. Liu L., Shack S., Stetler-Stevenson W.G., Hudgins W.R., Samid D. Differentiation of cultured human melanoma cells induced by the aromatic fatty acids phenylacetate and phenylbutyrate. J. Invest. Dermatol. 103:1994;335-340.
58. Newmark H.L., Young C.W. Butyrate and phenylacetate as differentiating agents: practical problems and opportunities. J. Cell Biochem. Suppl. 22:1995;247-253.
59. Wood C.G., Lee C., Grayhack J.T., Kozlowski J.M. Phenylacetate and phenylbutyrate promote cellular differentiation in human prostate cancer systems (Meeting abstract). Proc. Annu. Meet. Am. Assoc. Cancer Res. 35:1994;A2404.
60. Carducci M., Bowling M., Eisenberger M., Sinibaldi V., Simons J., Chen T., Noe D., Grochow L., Donehower R. Phenylbutyrate (PB) for refractory solid tumors: a phase I clinical and pharmacological evaluation. Proc. AACR. 39:1998;506.
61. Gore S.D., Weng L.J., Zhai S., Figg W.D., Donehower R.C., Dover G.J., Grever M., Griffin C.A., Grochow L.B., Rowinsky E.K., Zabalena Y., Hawkins A.L., Burks K., Miller C.B. Impact of the putative differentiating agent sodium phenylbutyrate on myelodysplastic syndromes and acute myeloid leukemia. Clin. Cancer Res. 7:2001;2330-2339.
62. Gilbert J., Baker S.D., Bowling M.K., Grochow L., Figg W.D., Zabelina Y., Donehower R.C., Carducci M.A. A phase I dose escalation and bioavailability study of oral sodium phenylbutyrate in patients with refractory solid tumor malignancies. Clin. Cancer Res. 7:2001;2292-2300.
63. Cheng S.H., Fang S.L., Zabner J., Marshall J., Piraino S., Schiavi S.C., Jefferson D.M., Welsh M.J., Smith A.E. Functional activation of the cystic fibrosis trafficking mutant ΔF508-CFTR by overexpression. Am. J. Physiol. 268:1995;L615-L624.
64. Rubenstein R.C., Egan M.E., Zeitlin P.L. In vitro pharmacologic restoration of CFTR-mediated chloride transport with sodium 4-phenylbutyrate in cystic fibrosis epithelial cells containing ΔF508-CFTR. J. Clin. Invest. 100:1997;2457-2465.
65. Rubenstein R.C., Zeitlin P.L. A pilot clinical trial of sodium 4-phenylbutyrate (buphenyl) in ΔF508-homozygous cystic fibrosis patients: evidence of restoration of nasal epithelial CFTR function. Am. J. Resp. Crit. Care Med. 157:1998;484-490.
66. Zeitlin P.L., Diener-West M., Rubenstein R.C., Boyle M.P., Lee C.K., Brass-Ernst L. Evidence of CFTR function in cystic fibrosis after systemic administration of 4-phenylbutyrate. Mol. Ther. 6:2002;119-126.
67. - secretion in Calu-3 airway epithelial cells. Am. J. Physiol. 277:1999;L700-L708.
68. Garcia-Bermejo L., Vilaboa N.E., Perez C., Galan A., De Blas E., Aller P. Modulation of heat-shock protein 70 (HSP70) gene expression by sodium butyrate in U-937 promonocytic cells: relationships with differentiation and apoptosis. Exp. Cell Res. 236:1997;268-274.
69. Lukacs G.L., Chang X.B., Bear C., Kartner N., Mohamed A., Riordan J.R., Grinstein S. The ΔF508 mutation decreases the stability of cystic fibrosis transmembrane conductance regulator in the plasma membrane. Determination of functional half-lives on transfected cells. J. Biol. Chem. 268:1993;21592-21598.
70. Heda G.D., Tanwani M., Marino C.R. The ΔF508 mutation shortens the biochemical half-life of plasma membrane CFTR in polarized epithelial cells. Am. J. Physiol Cell Physiol. 280:2001;C166-C174.
71. Sharma M., Benharouga M., Hu W., Lukacs G.L. Conformational and temperature-sensitive stability defects of the ΔF508 cystic fibrosis transmembrane conductance regulator in postendoplasmic reticulum compartments. J. Biol. Chem. 276:2001;8942-8950.
72. Grubb B., Lazarowski E., Knowles M., Boucher R. Isobutylmethylxanthine fails to stimulate chloride secretion in cystic fibrosis airway epithelia. Am. J. Respir. Cell Mol. Biol. 8:1993;454-460.
73. Eidelman O., Guay-Broder C., van Galen P.J., Jacobson K.A., Fox C., Turner R.J., Cabantchik Z.I., Pollard H.B. A1 adenosine-receptor antagonists activate chloride efflux from cystic fibrosis cells. Proc. Natl. Acad. Sci. USA. 89:1992;5562-5566.
74. Guay-Broder C., Jacobson K.A., Barnoy S., Cabantchik Z.I., Guggino W.B., Zeitlin P.L., Turner R.J., Vergara L., Eidelman O., Pollard H.B. A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine selectively activates chloride efflux from human epithelial and mouse fibroblast cell lines expressing the cystic fibrosis transmembrane regulator ΔF508 mutation. Biochemistry. 34:1995;9079-9087.
75. Arispe N., Ma J., Jacobson K.A., Pollard H.B. Direct activation of cystic fibrosis transmembrane conductance regulator channels by 8-cyclopentyl-1,3-dipropylxanthine (CPX) and 1,3-diallyl-8-cyclohexylzanthine (DAX). J. Biol. Chem. 273:1997;5727-5734.
76. Cohen B.E., Lee G., Jacobson K.A., Kim Y.C., Huang Z., Sorscher E.J., Pollard H.B. 8-Cyclopentyl-1,3-dipropylxanthine and other xanthines differentially bind to the wild-type and ΔF508 first nucleotide binding fold (NBF- (1) domains of the cystic fibrosis transmembrane conductance regulator. Biochemistry. 36:1997;6455-6461.
77. McCarty N.A., Standaert T.A., Teresi M., Tuthill C., Launspach J., Kelley T.J., Milgram L.J., Hilliard K.A., Regelmann W.E., Weatherly M.R., Aitken M.L., Konstan M.W., Ahrens R.C. A phase I randomized, multicenter trial of CPX in adult subjects with mild cystic fibrosis. Pediatr. Pulmonol. 33:2002;90-98.
78. Andersson C., Roomans G.M. Activation of ΔF508 CFTR in a cystic fibrosis respiratory epithelial cell line by 4-phenylbutyrate, genistein and CPX. Eur. Respir. J. 15:2000;937-941.
79. Kelley T.J., Al-Nakkash L., Drumm M.L. CFTR-mediated chloride permeability is regulated by type III phosphodiesterases in airway epithelial cells. Am. J. Respir. Cell Mol. Biol. 13:1995;657-664.
80. Kelley T.J., Al Nakkash L., Cotton C.U., Drumm M.L. Activation of endogenous ΔF508 cystic fibrosis transmembrane conductance regulator by phosphodiesterase inhibition. J. Clin. Invest. 98:1996;513-520.
81. Kelley T.J., Thomas K., Milgram L.J., Drumm M.L. In vivo activation of the cystic fibrosis transmembrane conductance regulator mutant ΔF508 in murine nasal epithelium. Proc. Natl. Acad. Sci. USA. 94:1997;2604-2608.
82. Illek B., Fischer H., Machen T.E. Alternate stimulation of apical CFTR by genistein in epithelia. Am. J. Physiol. 270:1996;C265-275.
83. Illek B., Fischer H. Flavonoids stimulate Cl conductance of human airway epithelium in vitro and in vivo. Am. J. Physiol. 275:1998;L902-L910.
84. Illek B., Zhang L., Lewis N.C., Moss R.B., Dong J.Y., Fischer H. Defective function of the cystic fibrosis-causing missense mutation G551D is recovered by genistein. Am. J. Physiol. 277:1999;C833-C839.
85. Reenstra W.W., Yurko-Mauro K., Dam A., Raman S., Shorten S. CFTR chloride channel activation by genistein: the role of serine/threonine protein phosphatases. Am. J. Physiol. 271:1996;C650-657.
86. Chiang C.E., Chen S.A., Chang M.S., Lin C.I., Luk H.N. Genistein directly induces cardiac CFTR chloride current by a tyrosine kinase-independent and protein kinase A-independent pathway in guinea pig ventricular myocytes. Biochem. Biophys. Res. Commun. 235:1997;74-78.
87. Randak C., Auerswald E.A., Assfalg-Machleidt I., Reenstra W.W., Machleidt W. Inhibition of ATPase, GTPase and adenylate kinase activities of the second nucleotide-binding fold of the cystic fibrosis transmembrane conductance regulator by genistein. Biochem. J. 340:(Pt 1):1999;227-235.
88. Tabary O., Escotte S., Couetil J.P., Hubert D., Dusser D., Puchelle E., Jacquot J. High susceptibility for cystic fibrosis human airway gland cells to produce IL-8 through the I κB kinase α pathway in response to extracellular NaCl content. J. Immunol. 164:2000;3377-3384.
89. Tabary O., Zahm J.M., Hinnrasky J., Couetil J.P., Cornillet P., Guenounou M., Gaillard D., Puchelle E., Jacquot J. Selective upregulation of chemokine IL-8 expression in cystic fibrosis bronchial gland cells in vivo and in vitro. Am. J. Pathol. 153:1998;921-930.
90. Tabary O., Escotte S., Couetil J.P., Hubert D., Dusser D., Puchelle E., Jacquot J. Relationship between IκBα deficiency, NFκB activity and interleukin-8 production in CF human airway epithelial cells. Pflugers Arch. 443:(Suppl 1):2001;S40-S44.
91. Tabary O., Escotte S., Couetil J.P., Hubert D., Dusser D., Puchelle E., Jacquot J. Genistein inhibits constitutive and inducible NFκB activation and decreases IL-8 production by human cystic fibrosis bronchial gland cells. Am. J. Pathol. 155:1999;473-481.
92. Suaud L., Li J., Jiang Q., Rubenstein R.C., Kleyman T.R. Genistein restores functional interactions between ΔF508-CFTR and ENaC in Xenopus oocytes. J. Biol. Chem. 277:2002;8928-8933.
93. Hansen R.K., Oesterreich S., Lemieux P., Sarge K.D., Fuqua S.A. Quercetin inhibits heat shock protein induction but not heat shock factor DNA-binding in human breast carcinoma cells. Biochem. Biophys. Res. Commun. 239:1997;851-856.
94. M. Lim, A. Floyd, P.L. Zeitlin, The Effects of Flavonoids in dF508 CFTR Processing (2002).
95. Galietta L.V., Jayaraman S., Verkman A.S. Cell-based assay for high-throughput quantitative screening of CFTR chloride transport agonists. Am. J. Physiol. Cell Physiol. 281:2001;C1734-C1742.