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

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 P.aeruginosa. Extracts and purified components have been added to cells 24h 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 antihelmintica 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 (IC(50)=200mug/ml) and Aegle marmelos (IC(50)=20mug/ml). Compounds from Aegle marmelos were isolated and identified by GC-MS. No significant effect was observed with butyl-p-tolyl-sulfate, 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 10muM 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.