title: Bergamot (Citrus bergamia Risso) fruit extracts and identified components alter expression of interleukin 8 gene in cystic fibrosis bronchial epithelial cell lines.
abstract: BACKGROUND
  Cystic fibrosis (CF) airway pathology is a fatal, autosomal, recessive genetic disease characterized by extensive lung inflammation. After induction by TNF-α, elevated concentrations of several pro-inflammatory cytokines (i.e. IL-6, IL-1β) and chemokines (i.e. IL-8) are released from airway epithelial cells. In order to reduce the excessive inflammatory response in the airways of CF patients, new therapies have been developed and in this respect, medicinal plant extracts have been studied. In this article we have investigated the possible use of bergamot extracts (Citrus bergamia Risso) and their identified components to alter the expression of IL-8 associated with the cystic fibrosis airway pathology.
  
  
  METHODS
  The extracts were chemically characterized by 1H-NMR (nuclear magnetic resonance), GC-FID (gas chromatography-flame ionization detector), GC-MS (gas chromatography-mass spectrometry) and HPLC (high pressure liquid chromatography). Both bergamot extracts and main detected chemical constituents were assayed for their biological activity measuring (a) cytokines and chemokines in culture supernatants released from cystic fibrosis IB3-1 cells treated with TNF-α by Bio-Plex cytokine assay; (b) accumulation of IL-8 mRNA by real-time PCR.
  
  
  RESULTS
  The extracts obtained from bergamot (Citrus bergamia Risso) epicarps contain components displaying an inhibitory activity on IL-8. Particularly, the most active molecules were bergapten and citropten. These effects have been confirmed by analyzing mRNA levels and protein release in the CF cellular models IB3-1 and CuFi-1 induced with TNF-α or exposed to heat-inactivated Pseudomonas aeruginosa.
  
  
  CONCLUSIONS
  These obtained results clearly indicate that bergapten and citropten are strong inhibitors of IL-8 expression and could be proposed for further studies to verify possible anti-inflammatory properties to reduce lung inflammation in CF patients.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Ferrara, Via Fossato di Mortara 74, Ferrara, 44121, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Borgatti
authors.forename: Irene
authors.initials: I
authors.lastname: Mancini
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Bianchi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Guerrini
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lampronti
authors.forename: Damiano
authors.initials: D
authors.lastname: Rossi
authors.forename: Gianni
authors.initials: G
authors.lastname: Sacchetti
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
mesh_terms: D001980:Bronchi / Q000473:pathology; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D002957:Citrus / Q000276:immunology; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005638:Fruit; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D016209:Interleukin-8; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha