title: Corilagin is a potent inhibitor of NF-kappaB activity and downregulates TNF-alpha induced expression of IL-8 gene in cystic fibrosis IB3-1 cells.
abstract: Corilagin (beta-1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-d-glucose), a gallotannin identified in several plants, including Phyllanthus urinaria, has been shown to exhibit versatile medicinal activities. As far as possible anti-inflammatory effects of corilagin, only few reports are available, and the potential use of corilagin as possible therapeutic molecule for cystic fibrosis has not been evaluated. In the present paper we report experiments aimed at determining the activity of corilagin on nuclear factor kappaB (NF-kappaB) binding to DNA target and on the expression of the major pro-inflammatory gene involved in cystic fibrosis, interleukin-8 (IL-8). Both IL-8 mRNA content and IL-8 protein secretion were analyzed in cystic fibrosis bronchial IB3-1 cells stimulated by tumor necrosis factor-alpha (TNF-alpha), one of the most potent pro-inflammatory agents. The data obtained demonstrate that corilagin binds to NF-kappaB, inhibits NF-kappaB/DNA interactions and affects IL-8 gene expression in TNF-alpha treated IB3-1 cells. In addition, corilagin inhibits TNF-alpha induced secretion of MCP-1 and RANTES, exhibiting low or no effect on the release of G-CSF, IL-6 and VEGF. Therefore, corilagin might be of interest for experimental anti-inflammatory therapy of cystic fibrosis.
authors.affiliation: BioPharmaNet, Department of Biochemistry and Molecular Biology, University of Ferrara, Via Fossato di Mortara 74, Ferrara, Italy. gam@unife.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
authors.forename: Monica
authors.initials: M
authors.lastname: Borgatti
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lampronti
authors.forename: Enrica
authors.initials: E
authors.lastname: Fabbri
authors.forename: Eleonora
authors.initials: E
authors.lastname: Brognara
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Bianchi
authors.forename: Laura
authors.initials: L
authors.lastname: Piccagli
authors.forename: Marcus Chun-Wah
authors.initials: MC
authors.lastname: Yuen
authors.forename: Chi-Wai
authors.initials: CW
authors.lastname: Kan
authors.forename: Desmond Kwok-Po
authors.initials: DK
authors.lastname: Hau
authors.forename: Wang-Fun
authors.initials: WF
authors.lastname: Fong
authors.forename: Wai-Yeung
authors.initials: WY
authors.lastname: Wong
authors.forename: Raymond Siu-Ming
authors.initials: RS
authors.lastname: Wong
authors.forename: Chung-Hin
authors.initials: CH
authors.lastname: Chui
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001483:Base Sequence; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D047348:Hydrolyzable Tannins; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C111835:CCL2 protein, human; C483024:CCL5 protein, human; C505032:CFTR protein, human; C508606:CXCL8 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D005960:Glucosides; D047348:Hydrolyzable Tannins; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C049096:corilagin