Cystic Fibrosis (CF) is the most diffuse autosomal recessive genetic disease affecting
Caucasians. A persistent recruitment of neutrophils in the bronchi of CF patients
contributes to exacerbate the airway tissue damage, suggesting that modulation of
chemokine expression may be an important target for the patient's well being thus
the identification of innovative anti-inflammatory drugs is considered a longterm
goal to prevent progressive tissue deterioration. Phloridzin, isolated from Malus
domestica by a selective molecular imprinting extraction, and its structural analogues,
Phloridzin heptapropionate (F1) and Phloridzin tetrapropionate (F2), were initially
investigated because of their ability to reduce IL-6 and IL-8 expression in human
CF bronchial epithelial cells (IB3-1) stimulated with TNF-α. Release of these cytokines
by CF cells was shown to be controlled by the Transcription Factor (TF) NF-kB. The
results of the present investigation show that of all the derivatives tested, Phloridzin
tetrapropionate (F2) is the most interesting and has greatest potential as it demonstrates
inhibitory effects on the expression and production of different cytokines involved
in CF inflammation processes, including RANTES, VEGF, GM-CSF, IL-12, G-CSF, MIP-1b,
IL-17, IL-10 and IP-10, without any correlated anti-proliferative and pro-apoptotic
effects.