Anti-inflammatory effects of azithromycin in cystic fibrosis airway epithelial cells

Cristina Cigana, Elena Nicolis, Matteo Pasetto, Baroukh Maurice Assael, Paola Melotti
Biochemical and Biophysical Research Communications 2006 December 1, 350 (4): 977-82
We aimed at identifying molecular mechanisms for anti-inflammatory effects of azithromycin (AZM) suggested by clinical evidences. IL-8 expression and DNA binding activity of two key pro-inflammatory transcription factors (TF), NF-kappaB and AP-1, were investigated in cystic fibrosis (CF) and isogenic non-CF airway epithelial cell lines. AZM reduced about 40% of IL-8 mRNA and protein expression (n=9, p=0.02, and n=4, p=0.00011) in CF cells reaching the levels of non-CF cells. In the presence of AZM we found about 50% and 70% reduction of NF-kappaB and AP-1 DNA binding, respectively (n=3, p=0.01, and n=3, p=0.0017), leading to levels of non-CF cells. The relevance of NF-kappaB and AP-1 in regulating IL-8 promoter transcriptional activity was demonstrated by gene reporter assays (n=4, p=8.54x10(-7), and n=4, p=6.45x10(-6)). Our data support the anti-inflammatory effects of AZM in CF cells, indicating inhibition of transcription of pro-inflammatory genes as possible mechanism, thus providing a rationale for the possible use of specific TF inhibitors for therapy.

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