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

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• 作者：Roberto Gambari^a ; ^gam@unife.it ; Monica Borgatti^a ; Ilaria Lampronti^a ; Enrica Fabbri^a ; Eleonora Brognara^a ; Nicoletta Bianchi^a ; Laura Piccagli^a ; Marcus Chun-Wah Yuen^b ; Chi-Wai Kan^b ; Desmond Kwok-Po Hau^c ; Wang-Fun Fong^c ; Wai-Yeung Wong^d ; Raymond Siu-Ming Wong^e ; Chung-Hin Chui^b ; ^e
• 关键词：CF ; cystic fibrosis ; TFD ; transcription factor decoy ; EMSA ; electrophoretic mobility shift assay ; TNF-alpha ; tumor necrosis factor alpha ; NF-kappaB ; nuclear factor kappaB ; IL-8 ; interleukin-8 ; IL-6 ; interleukin-6 ; G-CSF ; granulocyte colony-stimulating fac
• 刊名：International Immunopharmacology
• 出版年：2012
• 期刊代码：123_15675769
• 类别：med
• 出版时间：July, 2012
• 卷：13
• 期：3
• 页码：308-315
• 文件大小：588 K

摘要

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.