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.
Cystic fibrosis (CF) is a genetic disease characterized by chronic bacterial lung infection, most commonly sustained by Pseudomonas aeruginosa. Upon infection, elevated concentrations of pro-inflammatory cytokines (i.e. IL-6 and IL1beta) and chemokines (i.e. IL-8 and GROgamma) are found in the bronchoalveolar fluid of CF patients. We report in this paper that: (a) IL-8, IL-6, IL-1beta, ICAM-1, and GRO-gamma genes are upregulated following infection of CF bronchial epithelial IB3-1 cells with P. aeruginosa; (b) Sp1 transcription factor activity is induced following infection of the cystic fibrosis IB3-1 and CuFi-1 cell lines; (c) inhibition of Sp1 activity using transcription factor decoy molecules leads to inhibition of the expression of IL-6 gene. From the theoretical point of view, our results demonstrate that Sp1 transcription factor activity is induced following infection of CF cells with P. aeruginosa, and that this effect is important in the activation of IL-6 gene transcription. From the practical point of view, our data sustain the potential use of decoy molecules targeting the transcription factor Sp1 to control a relevant molecule involved in the inflammatory process associated with the cystic fibrosis airway pathology.
Borgatti
Monica
M
ER-GenTech, Department of Biochemistry and Molecular Biology, University of Ferrara, Via Fossato di Mortara, 74, 44100 Ferrara, Italy.
Bezzerri
Valentino
V
Mancini
Irene
I
Nicolis
Elena
E
Dechecchi
Maria Cristina
MC
Lampronti
Ilaria
I
Rizzotti
Paolo
P
Cabrini
Giulio
G
Gambari
Roberto
R
D001980:Bronchi / Q000276:immunology* / Q000382:microbiology*; D002460:Cell Line; D003550:Cystic Fibrosis / Q000276:immunology* / Q000382:microbiology*; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D016329:Sp1 Transcription Factor / Q000276:immunology*; D014157:Transcription Factors / Q000276:immunology*
C508600:IL6 protein, human; D015850:Interleukin-6; D016329:Sp1 Transcription Factor; D014157:Transcription Factors