title: Down-regulation of IL-8 expression in human airway epithelial cells through helper-dependent adenoviral-mediated RNA interference.
abstract: Interleukin (IL)-8 is a potent neutrophil chemotactic factor and a crucial mediator in neutrophil-dependent inflammation. Various cell types produce IL-8, either in response to external stimuli such as cytokines or bacterial infection, or after malignant transformation. Anti-IL-8 strategies have been considered for anti-inflammatory therapy. In this paper we demonstrate that the RNA interference technique can be used to efficiently down-regulate IL-8 protein expression in airway epithelial cells. We used a helper-dependent adenoviral vector to express a small hairpin (sh)RNA targeting human IL-8 in cultured airway epithelial cells (IB3-1, Cftr-/-; C38, Cftr-corrected) stimulated with TNF-alpha, IL-1beta or heat-inactivated Burkholderia cenocepacia. Stimulated IL-8 expression in IB3-1 and C38 cells was significantly reduced by shRNA expression. The shRNA targeting IL-8 had no effect on the activation of NF-kappaB, or on the protein levels of IkappaB or IL-6, suggesting that this anti-IL-8 strategy was highly specific, and therefore may offer potential for the treatment of inflammatory diseases.
authors.affiliation: Programme in Lung Biology Research and the Canadian Institutes of Health Research Group in Lung Development, Hospital for Sick Children, Toronto, Canada M5G 1X8.
authors.forename: Hui Bi
authors.initials: HB
authors.lastname: Cao
authors.forename: Anan
authors.initials: A
authors.lastname: Wang
authors.forename: Bernard
authors.initials: B
authors.lastname: Martin
authors.forename: David R
authors.initials: DR
authors.lastname: Koehler
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Zeitlin
authors.forename: A Keith
authors.initials: AK
authors.lastname: Tanawell
authors.forename: Jim
authors.initials: J
authors.lastname: Hu
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D019117:Burkholderia / Q000502:physiology; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology; D015536:Down-Regulation; D004847:Epithelial Cells / Q000276:immunology; D017930:Genes, Reporter; D006378:Helper Viruses / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D034622:RNA Interference; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology*
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B
references.citation: Nat Biotechnol. 2002 Oct;20(10):1006-10
references.pmid: 12244328
references.citation: J Clin Invest. 2001 Jan;107(1):13-9
references.pmid: 11134172
references.citation: Nature. 2000 Aug 17;406(6797):782-7
references.pmid: 10963608
references.citation: Methods. 2002 Feb;26(2):199-213
references.pmid: 12054897
references.citation: Clin Sci (Lond). 1992 Mar;82(3):273-5
references.pmid: 1312411
references.citation: Nature. 1998 Feb 19;391(6669):806-11
references.pmid: 9486653
references.citation: Annu Rev Immunol. 2003;21:335-76
references.pmid: 12524386
references.citation: Am J Physiol Lung Cell Mol Physiol. 2001 Mar;280(3):L493-502
references.pmid: 11159033
references.citation: Circulation. 2000 Apr 4;101(13):1519-26
references.pmid: 10747344
references.citation: Nihon Yakurigaku Zasshi. 2002 Aug;120(2):91-5
references.pmid: 12187627
references.citation: Am J Respir Crit Care Med. 1995 Dec;152(6 Pt 1):2111-8
references.pmid: 8520783
references.citation: Clin Genet. 2000 Jul;58(1):1-11
references.pmid: 10945654
references.citation: Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5515-20
references.pmid: 11960009
references.citation: Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1844-8
references.pmid: 12552109
references.citation: Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):6047-52
references.pmid: 11972060
references.citation: Infect Immun. 1997 Feb;65(2):617-22
references.pmid: 9009321
references.citation: Gene Ther. 2003 Jul;10(14):1135-41
references.pmid: 12833122
references.citation: Clin Cancer Res. 2003 Aug 1;9(8):3167-75
references.pmid: 12912969
references.citation: J Exp Med. 1994 Sep 1;180(3):1135-40
references.pmid: 8064229
references.citation: J Invest Dermatol. 2002 Jun;118(6):915-22
references.pmid: 12060384
references.citation: J Immunol. 2003 Mar 15;170(6):3369-76
references.pmid: 12626597
references.citation: Arterioscler Thromb Vasc Biol. 2004 Aug;24(8):1503-8
references.pmid: 15178568
references.citation: Am J Respir Cell Mol Biol. 2000 Sep;23(3):396-403
references.pmid: 10970832
references.citation: Nature. 2001 May 24;411(6836):494-8
references.pmid: 11373684
references.citation: J Clin Invest. 1995 Jan;95(1):89-103
references.pmid: 7814650
references.citation: Pediatr Res. 2003 Sep;54(3):297-305
references.pmid: 12761358
references.citation: Am J Physiol Lung Cell Mol Physiol. 2002 Oct;283(4):L690-9
references.pmid: 12225945
references.citation: Genome Res. 2003 Oct;13(10):2325-32
references.pmid: 12975310
references.citation: Clin Infect Dis. 2003 Oct 1;37 Suppl 3:S225-64
references.pmid: 12975753
references.citation: Eur J Pediatr. 1996 Feb;155(2):112-6
references.pmid: 8775225
references.citation: Am J Respir Crit Care Med. 2002 Nov 1;166(9):1248-56
references.pmid: 12403695
references.citation: J Intern Med. 2001 Aug;250(2):91-104
references.pmid: 11489059
references.citation: Am J Respir Crit Care Med. 1997 Oct;156(4 Pt 1):1197-204
references.pmid: 9351622
references.citation: Methods Mol Med. 2002;69:371-88
references.pmid: 11987790
references.citation: Nature. 1993 Oct 14;365(6447):654-7
references.pmid: 8413628
references.citation: J Virol. 2001 Oct;75(20):9896-908
references.pmid: 11559822
references.citation: Mol Ther. 2003 Nov;8(5):846-52
references.pmid: 14599819
references.citation: N Engl J Med. 1998 Feb 12;338(7):436-45
references.pmid: 9459648
references.citation: J Pharmacol Exp Ther. 2001 Oct;299(1):90-5
references.pmid: 11561067
references.citation: Mol Ther. 2001 Aug;4(2):84-91
references.pmid: 11482978
references.citation: Nature. 2002 Jul 25;418(6896):435-8
references.pmid: 12087358
references.citation: Am J Respir Crit Care Med. 2003 Dec 15;168(12):1471-5
references.pmid: 12969869
references.citation: Infect Immun. 2001 Aug;69(8):5138-50
references.pmid: 11447196
references.citation: Clin Exp Immunol. 2000 Nov;122(2):207-11
references.pmid: 11091276
references.citation: Science. 2000 Mar 31;287(5462):2431-3
references.pmid: 10766620
references.citation: Nat Genet. 1995 Apr;9(4):351-7
references.pmid: 7540910
references.citation: Am J Physiol Lung Cell Mol Physiol. 2002 Oct;283(4):L688-9
references.pmid: 12225944
references.citation: Am J Respir Cell Mol Biol. 1991 Apr;4(4):313-9
references.pmid: 1849726
references.citation: J Biol Chem. 1993 Feb 15;268(5):3781-90
references.pmid: 7679117
references.citation: Hum Gene Ther. 2002 Jan 1;13(1):129-41
references.pmid: 11779417
references.citation: Am J Physiol Lung Cell Mol Physiol. 2003 Apr;284(4):L566-77
references.pmid: 12618418
references.citation: Am J Physiol Regul Integr Comp Physiol. 2002 Apr;282(4):R1245-52
references.pmid: 11893631
references.citation: Proc Natl Acad Sci U S A. 2003 May 27;100(11):6343-6
references.pmid: 12730368
references.citation: Nat Rev Immunol. 2002 Sep;2(9):664-74
references.pmid: 12209135
references.citation: Methods Enzymol. 1990;181:3-19
references.pmid: 2381324
references.citation: Am J Respir Crit Care Med. 1999 Jul;160(1):186-91
references.pmid: 10390398
references.citation: Cytokine. 1994 Mar;6(2):162-70
references.pmid: 8031999
references.citation: Curr Pharm Des. 2003;9(1):1-5
references.pmid: 12570669
references.citation: J Leukoc Biol. 1999 Sep;66(3):401-10
references.pmid: 10496309
references.citation: J Biol Chem. 1999 Apr 16;274(16):10689-92
references.pmid: 10196138
references.citation: Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15364-9
references.pmid: 14673110
references.citation: Am J Physiol Lung Cell Mol Physiol. 2003 Feb;284(2):L307-15
references.pmid: 12388360
references.citation: Mol Med. 2001 Aug;7(8):523-34
references.pmid: 11591888
references.citation: FEBS Lett. 2003 Mar 27;539(1-3):111-4
references.pmid: 12650936
references.citation: Am J Respir Cell Mol Biol. 1998 Aug;19(2):210-5
references.pmid: 9698592
references.citation: Am J Pathol. 2002 Jul;161(1):125-34
references.pmid: 12107097