title: Modulation of expression of IL-8 gene in bronchial epithelial cells by 5-methoxypsoralen.
abstract: Persistent recruitment of neutrophils in the bronchi of cystic fibrosis patients contributes to airway tissue damage, suggesting the importance of intervening on the expression of the neutrophil chemokine IL-8. Extracts from plants have been investigated to select components able to reduce IL-8 expression in bronchial epithelial cells challenged with Pseudomonas aeruginosa. Extracts and purified components have been added to cells 24 h before pro-inflammatory challenge with P. aeruginosa and IL-8 transcription was quantified in the IB3-1 CF cells in vitro. P. aeruginosa-dependent IL-8 mRNA induction was increased by Argemone mexicana and Vernonia anthelmintica whereas no significant modification of transcription was observed with Aphanamixis polystachya, Lagerstroemia speciosa and Hemidesmus indicus. Finally, inhibition of IL-8 was observed with Polyalthia longifolia (IC50=200 microg/ml) and Aegle marmelos (IC50=20 microg/ml). Compounds from A. marmelos were isolated and identified by GC-MS. No significant effect was observed with butyl-p-tolyl sulphate, whereas the inhibition obtained with 6-methyl-4-chromanone concentration was accompanied by an anti-proliferative effect. On the contrary, 5-methoxypsoralen resulted in IL-8 inhibition at 10 microM concentration, without effects on cell proliferation. In synthesis, 5-methoxypsoralen can be taken into consideration to investigate mechanisms of neutrophil chemotactic signalling and for its potential application in modulating the excessive CF lung inflammation.
authors.affiliation: Laboratory of Molecular Pathology, University Hospital of Verona, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Nicolis
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lampronti
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Dechecchi
authors.forename: Monica
authors.initials: M
authors.lastname: Borgatti
authors.forename: Anna
authors.initials: A
authors.lastname: Tamanini
authors.forename: Valentino
authors.initials: V
authors.lastname: Bezzerri
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Bianchi
authors.forename: Martina
authors.initials: M
authors.lastname: Mazzon
authors.forename: Irene
authors.initials: I
authors.lastname: Mancini
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Giri
authors.forename: Paolo
authors.initials: P
authors.lastname: Rizzotti
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
authors.forename: Giulio
authors.initials: G
authors.lastname: Cabrini
mesh_terms: D000078223:5-Methoxypsoralen; D031674:Argemone; D001980:Bronchi / Q000473:pathology; D002460:Cell Line; D049109:Cell Proliferation; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008730:Methoxsalen / Q000008:administration & dosage / Q000031:analogs & derivatives; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D017319:Photosensitizing Agents / Q000008:administration & dosage; D010936:Plant Extracts; D011550:Pseudomonas aeruginosa / Q000276:immunology* / Q000472:pathogenicity; D035741:Vernonia
chemical_list: D016209:Interleukin-8; D017319:Photosensitizing Agents; D010936:Plant Extracts; D000078223:5-Methoxypsoralen; D008730:Methoxsalen