title: Phloridzin derivatives inhibiting pro-inflammatory cytokine expression in human cystic fibrosis IB3-1 cells.
abstract: 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.
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Section of Biochemistry and Molecular Biology, Via Fossato di Mortara 74, 44121 Ferrara, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Milani
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Section of Biochemistry and Molecular Biology, Via Fossato di Mortara 74, 44121 Ferrara, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Marcellini
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Section of Biochemistry and Molecular Biology, Via Fossato di Mortara 74, 44121 Ferrara, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Montagner
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Master Course in Cosmetic Sciences and Technology, Laboratory of Health Products, Via Fossato di Mortara 17/19, 44121 Ferrara, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Baldisserotto
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Master Course in Cosmetic Sciences and Technology, Laboratory of Health Products, Via Fossato di Mortara 17/19, 44121 Ferrara, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Manfredini
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Section of Biochemistry and Molecular Biology, Via Fossato di Mortara 74, 44121 Ferrara, Italy. Electronic address: gam@unife.it.
authors.forename: R
authors.initials: R
authors.lastname: Gambari
authors.affiliation: Department of Life Sciences and Biotechnology, University of Ferrara, Section of Biochemistry and Molecular Biology, Via Fossato di Mortara 74, 44121 Ferrara, Italy. Electronic address: lmi@unife.it.
authors.forename: I
authors.initials: I
authors.lastname: Lampronti
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003550:Cystic Fibrosis / Q000378:metabolism; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005638:Fruit; D006801:Humans; D027845:Malus; D016328:NF-kappa B / Q000378:metabolism; D010695:Phlorhizin / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D010936:Plant Extracts; D012333:RNA, Messenger; D004247:DNA; D010695:Phlorhizin
keywords: CF, Cystic Fibrosis; Inflammation; Malus domestica; NF-kB, Nuclear Factor-kappaB; Phloridzin heptapropionate; Phloridzin tetrapropionate