Targeting transcription factor activity as a strategy to inhibit pro-inflammatory genes involved in cystic fibrosis: Decoy oligonucleotides and low-molecular weight compounds

Current Medicinal Chemistry

Volumn 17, Issue 35, 2010, Pages 4392-4404

  Cabrini, G ^a   Bezzerri, V ^a   Mancini, I ^b   Nicolis, E ^a   Dechecchi, M C ^a   Tamanini, A ^a   Lampronti, I ^b   Piccagli, L ^b   Bianchi, N ^b   Borgatti, M ^b   Gambari, R ^b  

^a UNIVERSITY HOSPITAL OF VERONA   (Italy)

^b UNIVERSITY OF FERRARA   (Italy)

Author keywords

Chemokines; Cystic fibrosis; Cytokines; Decoy; Inflammation; Transcription factors

Indexed keywords

AURINTRICARBOXYLIC ACID; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 6; INTERLEUKIN 8; OLIGONUCLEOTIDE; PREGNANCY SPECIFIC BETA1 GLYCOPROTEIN; PYROGALLOL; RESVERATROL; TRANSCRIPTION FACTOR;

ARTICLE; BACTERIAL INFECTION; BINDING SITE; CHRONIC DISEASE; CYSTIC FIBROSIS; CYTOKINE RELEASE; DRUG INHIBITION; DRUG SCREENING; DRUG TARGETING; EPITHELIUM CELL; GENE EXPRESSION; GENE SEQUENCE; HUMAN; MOLECULAR MECHANICS; NEUTROPHIL CHEMOTAXIS; NONHUMAN; PATHOPHYSIOLOGY; PNEUMONIA; PSEUDOMONAS AERUGINOSA; RESPIRATORY FAILURE; TISSUE INJURY; UPREGULATION;

ANIMALS; ANTI-INFLAMMATORY AGENTS; CYSTIC FIBROSIS; HUMANS; INFLAMMATION; INTERLEUKIN-8; MOLECULAR WEIGHT; NF-KAPPA B; OLIGONUCLEOTIDES; TRANSCRIPTION FACTORS;

EID: 78650648443     PISSN: 09298673     EISSN: None     Source Type: Journal    
DOI: 10.2174/092986710793361243     Document Type: Article

References (91)

1. Boucher, R. C. New concepts of the pathogenesis of cystic fibrosis lung disease. Eur. Respir. J., 2004, 23, 146-158.
2. Verkman, A. S.; Song, Y.; Thiagarajah, J. R. Role of airway surface liquid and submucosal glands in cystic fibrosis lung disease. Am. J. Physiol. Cell Physiol., 2003, 284, C2-15.
3. Machen, T. E. Am. J. Physiol. Cell. Physiol. Innate immune response in CF airway epithelia: hyperinflammatory? 2006, 291, C218-230.
4. Puchelle, E.; De Bentzmann, S.; Hubeau, C.; Jacquot, J.; Gaillard, D. Mechanisms involved in cystic fibrosis airway inflammation. Pediatr. Pulmonol., 2001, S23, 143-145.
5. Bonfield, T. L.; Panuska, J. R.; Konstan, M. W.; Hilliard, K. A.; Hilliard, J. B.; Ghnaim, H.; Berger, M. Inflammatory cytokines in cystic fibrosis lungs. Am. J. Respir. Crit. Care Med., 1995, 152, 2111-2118.
6. Khan, T. Z.; Wagener, J. S.; Bost, T.; Martinez, J.; Accurso, F. J.; Riches, D. W. Early pulmonary inflammation in infants with cystic fibrosis. Am. J. Respir. Crit. Care Med., 1995, 151, 1075-1082.
7. Mall, M. A.; Harkema, J. R.; Trojanek, J. B.; Treis, D.; Livraghi, A.; Schubert, S.; Zhou, Z.; Kreda, S. M.; Tilley, S. L.; Hudson, E. J.; O'Neal, W. K.; Boucher, R. C. Development of chronic bronchitis and emphysema in beta-epithelial Na+ channel-overexpressing mice. Am. J. Respir. Crit. Care Med., 2008, 177, 730-742.
8. Tirouvanziam, R.; de Bentzmann, S.; Hubeau, C.; Hinnrasky, J.; Jacquot, J.; Péault, B.; Puchelle, E. Inflammation and infection in naive human cystic fibrosis airway grafts. Am. J. Respir. Cell. Mol. Biol., 2000, 23, 121-127.
9. Muhlebach, M. S.; Reed, W.; Noah, T. L. Quantitative cytokine gene expression in CF airway. Pediatr. Pulmonol., 2004, 37, 393-399.
10. DiMango, E.; Ratner, A. J.; Bryan, R.; Tabibi, S.; Prince, A. Activation of NF-kappaB by adherent Pseudomonas aeruginosa in normal and cystic fibrosis respiratory epithelial cells. J. Clin. Invest., 1998, 101, 2598-2605.
11. Roum, J. H.; Buhl, R.; McElvaney, N. G.; Borok, Z.; Crystal, R. G. Systemic deficiency of glutathione in cystic fibrosis. J. Appl. Physiol., 1993, 75, 2419-2424.
12. Boucher, R. C. Evidence for airway surface dehydration as the initiating event in CF airway disease. J. Intern. Med., 2007, 261, 5-16.
13. Teichgraber, V.; Ulrich, M.; Endlich, N.; Riethmuller, J.; Wilker, B.; De Oliveira-Munding, C. C.; van Heeckeren, A. M.; Barr, M. L.; von Karthy, G.; Schmid, K. W.; Weller, M.; Tummler, B.; Lang, F.; Grassme, H.; Doring, G.; Gulbins, E. Ceramide accumulation mediates inflammation, cell death and infection susceptibility in cystic fibrosis. Nat. Med., 2008, 14, 382-391.
14. Di, A.; Brown, M. E.; Deriy, L. V.; Li, C.; Szeto, F. L.; Chen, Y.; Huang, P.; Tong, J.; Naren, A. P.; Bindokas, V.; Palfrey, H. C.; Nelson, D. J. CFTR regulates phagosome acidification in macrophages and alters bactericidal activity. Nat. Cell. Biol., 2006, 8, 933-944.
15. Ribeiro, C. M.; Paradiso, A. M.; Schwab, U.; Perez-Vilar, J.; Jones, L.; O'neal, W.; Boucher, R. C. Chronic airway infection/inflammation induces a Ca2+i-dependent hyperinflammatory response in human cystic fibrosis airway epithelia. J. Biol. Chem., 2005, 280, 17798-17806.
16. Haggie, P. M.; Verkman, A. S. Defective organellar acidification as a cause of cystic fibrosis lung disease: reexamination of a recurring hypothesis. Am. J. Physiol. Lung. Cell Mol. Physiol., 2009, 296, L859-867.
17. Bartling, T. R.; Drumm. M. L. Oxidative stress causes IL8 promoter hyperacetylationin cystic fibrosis airway cell models. Am. J. Respir. Cell Mol. Biol., 2009, 40, 58-65.
18. Brinkmann, V.; Reichard, U.; Goosmann, C.; Fauler, B.; Uhlemann, Y.; Weiss, D. S.; Weinrauch, Y.; Zychlinsky, A. Neutrophil extracellular traps kill bacteria. Science, 2004, 303, 1532-1535.
19. Myerburg, M. M.; McKenna, E. E.; Luke, C. J.; Frizzell, R. A.; Kleyman, T. R.; Pilewski, J. M. Prostasin expression is regulated by airway surface liquid volume and is increased in cystic fibrosis. Am. J. Physiol. Lung Cell. Mol. Physiol., 2008, 294, L932-941.
20. Diakov, A.; Bera, K.; Mokrushina, M.; Krueger, B.; Korbmacher, C. Cleavage in the {gamma}-subunit of the epithelial sodium channel (ENaC) plays an important role in the proteolytic activation of near-silent channels. J. Physiol., 2008, 586, 4587-4608.
21. Hartl, D.; Latzin, P.; Hordijk, P.; Marcos, V.; Rudolph, C.; Woischnik, M.; Krauss-Etschmann, S.; Koller, B.; Reinhardt, D.; Roscher, A. A.; Roos, D.; Griese, M. Cleavage of CXCR1 on neutrophils disables bacterial killing in cystic fibrosis lung disease. Nat. Med., 2007, 13, 1423-1430.
22. Downey, D. G.; Bell, S. C.; Elborn, J. S. Neutrophils in cystic fibrosis. Thorax, 2009, 64, 81-88.
23. Dubin, P. J.; Kolls, J. K. IL-23 mediates inflammatory responses to mucoid Pseudomonas aeruginosa lung infection in mice. Am. J. Physiol. Lung Cell. Mol. Physiol., 2007, 292, L519-28.
24. Dubin, P. J.; McAllister, F.; Kolls, J. K. Is cystic fibrosis a TH17 disease? Inflamm. Res., 2007, 56, 221-227.
25. Finder, J. D.; Pilewski, J. M.; Carreno, B. M.; Goldman, S. J.; Pirhonen, J.; Kolls, J. K. Role of IL-17A, IL-17F, and the IL-17 receptor in regulating growth-related oncogene-alpha and granulocyte colonystimulating factor in bronchial epithelium: implications for airway inflammation in cystic fibrosis. J. Immunol., 2005, 175, 404-412.
26. Aujla, S. J.; Dubin, P. J.; Kolls, J. K. Interleukin-17 in pulmonary host defense. Exp. Lung Res., 2007, 33, 507-518.
27. Nembrini, C.; Marsland, B. J.; Kopf, M. IL-17-producing T cells in lung immunity and inflammation. J. Allergy Clin. Immunol., 2009, 123, 986-994.
28. Jones, A. M.; Martin, L.; Bright-Thomas, R. J.; Dodd, M. E.; McDowell, A.; Moffitt, K. L.; Elborn, J. S.; Webb, A. K. Inflammatory markers in cystic fibrosis patients with transmissible Pseudomonas aeruginosa. Eur. Respir. J., 2003, 22, 503-506.
29. Becker, M. N.; Sauer, M. S.; Muhlebach, M. S.; Hirsh, A. J.; Wu, Q.; Verghese, M. W.; Randell, S. H. Cytokine secretion by cystic fibrosis airway epithelial cells. Am. J. Respir. Crit. Care Med., 2004, 169, 645-653.
30. Koehler, D. R.; Downey, G. P.; Sweezey, N. B.; Tanswell, A. K.; Hu. Lung inflammation as a therapeutic target in cystic fibrosis. J. Am. J. Respir. Cell Mol. Biol., 2004, 31, 377-381.
31. Bezzerri, V.; Borgatti, M.; Nicolis, E.; Lampronti, I.; Dechecchi, M. C.; Mancini, I.; Rizzotti, P.; Gambari, R.; Cabrini, G. Transcription factor oligodeoxynucleotides to NF-kappaB inhibit transcription of IL-8 in bronchial cells. Am. J. Respir. Cell Mol. Biol., 2008, 39, 86-96.
32. Borgatti, M.; Bezzerri, V.; Mancini, I.; Nicolis, E.; Dechecchi, M. C.; Lampronti, I.; Rizzotti, P.; Cabrini, G.; Gambari, R. Induction of IL-6 gene expression in a CF bronchial epithelial cell line by Pseudomonas aeruginosa is dependent on transcription factors belonging to the Sp1 superfamily. Biochem. Biophys. Res. Commun., 2007, 357, 977-983.
33. Anisowicz, A.; Messineo, M.; Lee, S. W.; Sager, R. An NF-kappa B-like transcription factor mediates IL-1/TNF-alpha induction of gro in human fibroblasts. J. Immunol., 1991, 147, 520-527.
34. Vij, N.; Amoako, M. O.; Mazur, S.; Zeitlin, P. L. CHOP transcription factor mediates IL-8 signaling in cystic fibrosis bronchial epithelial cells. Am. J. Respir. Cell. Mol. Biol., 2008, 38, 176-184.
35. Escotte, S.; Tabary, O.; Dusser, D.; Majer-Teboul, C.; Puchelle, E.; Jacquot. Fluticasone reduces IL-6 and IL-8 production of cystic fibrosis bronchial epithelial cells via IKK-beta kinase pathway. J. Eur. Respir. J., 2003, 21, 574-581.
36. Zeitlin, P. L.; Lu, L.; Rhim, J.; Cutting, G.; Stetten, G.; Kieffer, K. A.; Craig, R.; Guggino, W. B. A cystic fibrosis bronchial epithelial cell line: immortalization by adeno-12-SV40 infection. Am. J. Respir. Cell. Mol. Biol., 1991, 4, 313-319.
37. Zabner, J.; Karp, P.; Seiler, M.; Phillips, S. L.; Mitchell, C. J.; Saavedra, M.; Welsh, M.; Klingelhutz, A. Development of cystic fibrosis and noncystic fibrosis airway cell lines. J. Am. J. Physiol. Lung Cell Mol. Physiol., 2003, 284, L844-854.
38. Finkbeiner, W. E.; Carrier, S. D.; Teresi, C. E. Reverse transcriptionpolymerase chain reaction (RT-PCR) phenotypic analysis of cell cultures of human tracheal epithelium, tracheobronchial glands, and lung carcinomas. Am. J. Respir. Cell. Mol. Biol., 1993, 9, 547-556.
39. DiMango, E.; Ratner, A. J.; Bryan, R.; Tabibi, S.; Prince, A. Activation of NF-kappaB by adherent Pseudomonas aeruginosa in normal and cystic fibrosis respiratory epithelial cells. J. Clin. Invest., 1998, 101, 2598-2605.
40. Adamo, R.; Sokol, S.; Soong, G.; Gomez, M. I.; Prince, A. Pseudomonas aeruginosa flagella activate airway epithelial cells through asialoGM1 and Toll-Like Receptor 2 as well as toll-like receptor 5. Am. J. Respir. Cell Mol. Biol., 2004, 30, 627-634.
41. Saiman, L.; Prince, A. Pseudomonas aeruginosa pili bind to asialoGM1 which is increased on the surface of cystic fibrosis epithelial cells. J. Clin. Invest., 1993, 92, 1875-1880.
42. Dechecchi, M. C.; Nicolis, E.; Bezzerri, V.; Vella, A.; Colombatti, M.; Assael, B. M.; Mettey, Y.; Borgatti, M.; Mancini, I.; Gambari, R.; Becq, F.; Cabrini, G. Am. J. Respir. Cell. Mol. Biol., 2007, 36, 615-624.
43. Dzau, V. J. Transcription factor decoy. Circ. Res., 2002, 90, 1234-1236.
44. Mann, M. J.; Dzau, V. J. Therapeutic applications of transcription factor decoy oligonucleotides. J. Clin. Invest., 2000, 106, 1071-1075.
45. Morishita, R.; Sugimoto, T.; Aoki, M.; Kida, I.; Tomita, N.; Moriguchi, A.; Maeda, K.; Sawa, Y.; Kaneda, Y.; Higaki, J.; Ogihara, T. In vivo transfection of cis element "decoy" against nuclear factor-kappaB binding site prevents myocardial infarction. Nat. Med., 1997, 3, 894-899.
46. Tomita, T.; Takano, H.; Tomita, N.; Morishita, R.; Kaneko, M.; Shi, K.; Takahi, K.; Nakase, T.; Kaneda, Y.; Yoshikawa, H.; Ochi, T. Transcription factor decoy for NFkB inhibits cytokine and adhesion molecule expressions in synovial cells derived from rheumatoid arthritis. Rheumatology (Oxford), 2000, 39, 749-757.
47. Borgatti, M.; Lampronti, I.; Romanelli, A.; Pedone, C.; Saviano, M.; Bianchi, N.; Mischiati, C.; Gambari, R. Transcription factor decoy molecules based on a peptide nucleic acid (PNA)-DNA chimera mimicking Sp1 binding sites. J. Biol. Chem., 2003, 278, 7500-7509.
48. Penolazzi, L.; Lambertini, E.; Borgatti, M.; Piva, R.; Cozzani, M.; Giovannini, I.; Naccari, R.; Siciliani, G.; Gambari, R. Decoy oligodeoxynucleotides targeting NF-kappaB transcription factors: induction of apoptosis in human primary osteoclasts. Biochem. Pharmacol., 2003, 66, 1189-1198.
49. Piva, R.; Penolazzi, L.; Lambertini, E.; Giordano, S.; Gambari, R. Induction of apoptosis of human primary osteoclasts treated with a transcription factor decoy mimicking a promoter region of estrogen receptor alpha. Apoptosis, 2005, 10, 1079-1094.
50. Piva, R.; Penolazzi, L.; Zennaro, M.; Bianchini, E.; Magri, E.; Borgatti, M.; Lampronti, I.; Lambertini, E.; Tavanti, E.; Gambari, R. Induction of apoptosis of osteoclasts by targeting transcription factors with decoy molecules. Ann. N. Y. Acad. Sci., 2006, 1091, 509-516.
51. Penolazzi, L.; Borgatti, M.; Lambertini, E.; Mischiati, C.; Finotti, A.; Romanelli, A.; Saviano, M.; Pedone, C.; Piva, R.; Gambari, R. Peptide nucleic acid-DNA decoy chimeras targeting NF-kappaB transcription factors: Induction of apoptosis in human primary osteoclasts. Int. J. Mol. Med., 2004, 14, 145-152.
52. Lambertini, E.; Penolazzi, L.; Tavanti, E.; Pocaterra, B.; Schincaglia, G. P.; Torreggiani, E.; Franceschetti, T.; Vecchiattini, R.; Gambari, R.; Piva, R. Modulation of expression of specific transcription factors involved in the bone microenvironment. Minerva Biotecnologica, 2008, 20, 69-78.
53. Borgatti, M.; Bezzerri, V.; Mancini, I.; Nicolis, E.; Dechecchi, MC.; Rizzotti, P.; Lampronti, I.; Rizzotti, P.; Gambari, R.; Cabrini, G. Silencing of genes coding for transcription factors: biological effects of decoy oligonucleotides on cystic fibrosis bronchial epithelial cells. Minerva Biotecnologica, 2008, 20, 79-84.
54. Romanelli, A.; Pedone, C.; Saviano, M.; Bianchi, N.; Borgatti, M.; Mischiati, C.; Gambari, R. Molecular interactions with nuclear factor kappaB (NF-kappaB) transcription factors of a PNA-DNA chimera mimicking NF-kappaB binding sites. Eur. J. Biochem., 2001, 268, 6066-6075.
55. Borgatti, M.; Boyd, D. D.; Lampronti, I.; Bianchi, N.; Fabbri, E.; Saviano, M.; Romanelli, A.; Pedone, C.; Gambari, R. Decoy molecules based on PNA-DNA chimeras and targeting Sp1 transcription factors inhibit the activity of urokinase-type plasminogen activator receptor (uPAR) promoter. Oncol. Res., 2005, 15, 373-383.
56. Mann, M. J. Transcription factor decoys: a new model for disease intervention. Ann. N. Y. Acad. Sci., 2005, 1058, 128-139.
57. Cooper, J. A., Jr.; Parks, J. M.; Carcelen, R.; Kahlon, S. S.; Sheffield, M.; Culbreth, R. Attenuation of interleukin-1 induced monocyte interleukin-8 production by inhibiting nuclear factor kappa B translocation using decoy oligonucleotides. Biochem. Pharmacol., 2000, 59, 605-613.
58. Griesenbach, U.; Scheid, P.; Hillery, E.; de Martin, R.; Huang, L.; Geddes, D. M.; Alton, E. W. Anti-inflammatory gene therapy directed at the airway epithelium. Gene Ther., 2000, 7, 306-313.
59. Escobar-Díaz, E.; López-Martín, E. M.; Hernández del Cerro, M.; Puig-Kroger, A.; Soto-Cerrato, V.; Montaner, B.; Giralt, E.; García-Marco, J. A.; Pérez-Tomás, R.; Garcia-Pardo, A. AT514, a cyclic depsipeptide from Serratia marcescens, induces apoptosis of B-chronic lymphocytic leukemia cells: interference with the Akt/NF-kappaB survival pathway. Leukemia, 2005, 19, 572-579.
60. Talhouk, R. S.; Karam, C.; Fostok, S.; El-Jouni, W.; Barbour, E. K. Anti-inflammatory bioactivities in plant extracts. J. Med. Food. 2007, 10, 1-10.
61. Michael, R. E.; Nathan W. B.; Clarke, D.; Birrell, M.; Belvisi, M.; Johnston, S. L. Targeting the NF-κB pathway in asthma and chronic obstructive pulmonary disease. Pharmacol. Therap., 2009, 121, 1-13.
62. Sharma, R. K.; Garg, B. S.; Kurosaki, H.; Goto, M.; Otsuka, M.; Yamamoto, T.; Inoue, J. Aurine tricarboxylic acid, a potent metalchelating inhibitor of NFkappaB-DNA binding. Bioorg. Med. Chem., 2000, 8, 1819-1823.
63. Sharma, R. K.; Pande, V.; Ramos, M. J.; Rajor, H. K.; Chopra, S.; Meguro, K.; Inoue, J.; Otsuka, M. Bioorg. Chem., 2005, 33, 67-81.
64. Sharma, R. K.; Otsuka, M.; Pande, V.; Inoue, J.; Joao Ramos, M. Inhibitory activity of polyhydroxycarboxylate chelators against recombinant NF-kappaB p50 protein-DNA binding. Bioorg. Med. Chem. Lett., 2004, 14, 6123-6127.
65. Jeandet, P.; Bessis, R.; Gautheron, B. Production of resveratrol (3, 5, 4'-trihydroxystilbene) by grape berries in different developmental stages. Am. J. Enol. Vitic., 1991, 42, 41-46.
66. Carbo, N.; Costelli, P.; Baccino, F. M.; Lopez-Soriano, F. J.; Argiles, J. M. Resveratrol, a natural product present in wine, decreases tumour growth in a rat tumour model. Biochem. Biophys. Res. Commun., 1999, 254, 739-743.
67. Paul, B.; Masih, I.; Deopujari, J.; Charpentier, C. Occurrence of resveratrol and pterostilbene in age-old darakchasava, an ayurvedic medicine from India. J. Ethnopharmacol., 1999, 68, 71-76.
68. Zaidi, S. F.; Ahmed, K.; Yamamoto, T.; Kondo, T.; Usmanghani, K.; Kadowaki, M.; Sugiyama, T. Effect of resveratrol on helicobacter pylori-induced interleukin-8 secretion, reactive oxygen species generation and morphological changes in human gastric epithelial cells. Biol. Pharm. Bull., 2009, 32, 1931-1935.
69. Ma, Z. H.; Ma, Q. Y.; Wang, L. C.; Sha, H. C.; Wu, S. L.; Zhang, M. Effect of resveratrol on NF-kappaB activity in rat peritoneal macrophages. Am. J. Chin. Med., 2006, 34, 623-630.
70. Kundu, J. K.; Shin, Y. K.; Kim, S. H.; Surh, Y. J. Resveratrol inhibits phorbol ester-induced expression of COX-2 and activation of NFkappaB in mouse skin by blocking IkappaB kinase activity. Carcinogenesis, 2006, 27, 1465-1474.
71. Shakibaei, M.; Csaki, C.; Nebrich, S.; Mobasheri, A. Resveratrol suppresses interleukin-1beta-induced inflammatory signaling and apoptosis in human articular chondrocytes: potential for use as a novel nutraceutical for the treatment of osteoarthritis. Biochem. Pharmacol., 2008, 76, 1426-1439.
72. Kubota, S.; Kurihara, T.; Mochimaru, H.; Satofuka, S.; Noda, K.; Ozawa, Y.; Oike, Y.; Ishida, S.; Tsubota, K. Prevention of ocular inflammation in endotoxin-induced uveitis with resveratrol by inhibiting oxidative damage and nuclear factor-kappaB activation. Invest. Ophthalmol. Vis. Sci., 2009, 50, 3512-3519.
73. Penolazzi L, Lambertini E, Tavanti E, Torreggiani E, Vesce F, Gambari R, Piva R. Evaluation of chemokine and cytokine profiles in osteoblast progenitors from umbilical cord blood stem cells by BIO-PLEX technology. Cell Biol. Int. 2008, 32, 320-5.
74. Lampronti, I.; Khan, M. T.; Borgatti, M.; Bianchi, N.; Gambari, R. Inhibitory effects of bangladeshi medicinal plant extracts on interactions between transcription factors and target DNA sequences. Evid. Based Complement. Alternat. Med., 2008, 5, 303-312.
75. Asmawi, M. Z.; Kankaanranta, H.; Moilanen, E.; Vapaatalo, H. Anti-inflammatory activities of Emblica officinalis Gaertn leaf extracts. J. Pharm. Pharmacol., 1993, 45, 581-584.
76. Nicolis, E.; Lampronti, I.; Dechecchi, M. C.; Borgatti, M.; Tamanini, A.; Bianchi, N.; Bezzerri, V.; Mancini, I.; Grazia Giri, M.; Rizzotti, P.; Gambari, R.; Cabrini, G. Pyrogallol, an active compound from the medicinal plant Emblica officinalis, regulates expression of pro-inflammatory genes in bronchial epithelial cells. Int. Immunopharmacol., 2008, 8, 1672-1680.
77. Sharma, R. K.; Chopra, S.; Sharma, S. D.; Pande, V.; Ramos, M. J.; Meguro, K.; Inoue, J.; Otsuka, M. Biological evaluation, chelation, and molecular modeling studies of novel metal-chelating inhibitors of NF-kappaB-DNA binding: structure activity relationships. J. Med. Chem., 2006, 49, 3595-3601.
78. Pande, V.; Sharma, R. K.; Inoue, J.; Otsuka, M.; Ramos, M. J. A molecular modeling study of inhibitors of nuclear factor kappa-B (p50)-DNA binding. J. Comput. Aided Mol. Des., 2003, 17, 825-836.
79. Piccagli, L.; Fabbri, E.; Borgatti, M.; Bezzerri, V.; Mancini, I.; Nicolis, E.; Dechecchi, M. C.; Lampronti, I.; Cabrini, G.; Gambari. R. Docking of molecules identified in bioactive medicinal plants extracts into the p50 NF-κB transcription factor: correlation with inhibition of NF-κB/DNA interactions and inhibitory effects on IL-8 gene expression. BMC Struct. Biol., 2008, 8, 38.
80. Piccagli, L., Fabbri, E., Borgatti, M., Bianchi, N., Bezzerri, V., Mancini, I., Nicolis, E., Dechecchi, C. M., Lampronti, I., Cabrini, G., Gambari, R. Virtual screening against p50 NF-kappaB transcription factor for the identification of inhibitors of the NFkappaB-DNA interaction and expression of NF-kappaB upregulated genes. ChemMedChem. 2009, 4, 2024-33.
81. Gambari, R. Predictive analyses of biological effects of natural products: from plant extracts to biomolecular laboratory and computer modeling. Evid. Based Complement Alternat. Med., 2009, Sep. 14.
82. Rollinger, J. M.; Schuster, D.; Danzl, B.; Schwaiger, S.; Markt, P.; Schmidtke, M.; Gertsch, J.; Raduner, S.; Wolber, G.; Langer, T., Stuppner, H. In silico target fishing for rationalized ligand discovery exemplified on constituents of Ruta graveolens. Planta Med., 2009, 75, 195-204.
83. Chen, C. Y.; Chen, Y. F.; Tsai, H. Y. What is the effective component in suanzaoren decoction for curing insomnia? Discovery by virtual screening and molecular dynamic simulation. J. Biomol. Struct. Dyn., 2008, 26, 57-64.
84. Rollinger, J. M.; Langer, T.; Stuppner, H. Integrated in silico tools for exploiting the natural products' bioactivity. Planta Med., 2006, 72, 671-678.
85. Rollinger, J. M.; Langer, T.; Stuppner, H. Strategies for efficient lead structure discovery from natural products. Curr. Med. Chem., 2006, 13, 1491-507.
86. Mischiati, C.; Borgatti, M.; Bianchi, N.; Rutigliano, C.; Tomassetti, M.; Feriotto, G.; Gambari, R. Interaction of the human NF-kappaB p52 transcription factor with DNA-PNA hybrids mimicking the NF-kappaB binding sites of the human immunodeficiency virus type 1 promoter. J. Biol. Chem., 1999, 274, 33114-33122.
87. Gambari, R. Biological activity and delivery of peptide nucleic acids (PNA)-DNA chimeras for transcription factor decoy (TFD) pharmacotherapy. Curr. Med. Chem., 2004, 11, 1253-1263.
88. Saviano, M.; Romanelli, A.; Bucci, E.; Pedone, C.; Mischiati, C.; Bianchi, N.; Feriotto, G.; Borgatti, M.; Gambari, R. Computational procedures to explain the different biological activity of DNA/DNA, DNA/PNA and PNA/PNA hybrid molecules mimicking NF-kappaB binding sites. J. Biomol. Struct. Dyn., 2000, 18, 353-362.
89. Romanelli, A.; Pedone, C.; Saviano, M.; Bianchi, N.; Borgatti, M.; Mischiati, C.; Gambari, R. Molecular interactions with nuclear factor kappaB (NF-kappaB) transcription factors of a PNA-DNA chimera mimicking NF-kappaB binding sites. Eur. J. Biochem., 2001, 268, 6066-6075.
90. Borgatti, M.; Lampronti, I.; Romanelli, A.; Pedone, C.; Saviano, M.; Bianchi, N.; Mischiati, C.; Gambari, R. Transcription factor decoy molecules based on a peptide nucleic acid (PNA)-DNA chimera mimicking Sp1 binding sites. J. Biol. Chem., 2003, 278, 7500-7509.
91. Borgatti, M.; Breda, L.; Cortesi, R.; Nastruzzi, C.; Romanelli, A.; Saviano, M.; Bianchi, N.; Mischiati, C.; Pedone, C.; Gambari, R. Cationic liposomes as delivery systems for double-stranded PNADNA chimeras exhibiting decoy activity against NF-kappaB transcription factors. Biochem. Pharmacol., 2002, 64, 609-616.