Modulation of expression of IL-8 gene in bronchial epithelial cells by 5-methoxypsoralen

Int Immunopharmacol. 2009 Nov;9(12):1411-22. doi: 10.1016/j.intimp.2009.08.013. Epub 2009 Aug 29.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Methoxypsoralen
  • Argemone*
  • Bronchi / pathology
  • Cell Line
  • Cell Proliferation
  • Cystic Fibrosis / drug therapy
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis / immunology
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism*
  • Gene Expression Regulation
  • Humans
  • Interleukin-8 / genetics
  • Interleukin-8 / immunology
  • Interleukin-8 / metabolism*
  • Methoxsalen / administration & dosage
  • Methoxsalen / analogs & derivatives
  • Neutrophils / drug effects
  • Neutrophils / pathology
  • Photosensitizing Agents / administration & dosage
  • Plant Extracts
  • Pseudomonas aeruginosa / immunology*
  • Pseudomonas aeruginosa / pathogenicity
  • Vernonia*

Substances

  • Interleukin-8
  • Photosensitizing Agents
  • Plant Extracts
  • 5-Methoxypsoralen
  • Methoxsalen