Effects of glucocorticosteroids and antimicrobial drugs on inhibition of IL-1-beta and PDBu-induced IL-8 release in the presence of pyocyanin in bronchial epithelial cell line

Abstract

Pyocyanin, a blue phenazine pigment produced by Pseudomonas aeruginosa, has been shown to stimulate the release of interleukin (IL)-8 in airway epithelium directly, as well as synergising with IL-1 in triggering IL-8 release. IL-8 is a potent chemoattractant accounting for the neutrophilic influx in the pathogenesis of bronchiectasis. We investigated the effects of pyocyanin, alone and in combination, with IL-1β and phorbol 12,13-dibutyrate (PDBu) on IL-8 mRNA and release in BEAS-2B cells by reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Pyocyanin alone produced no increase in IL-8 mRNA or protein but caused significant dose-dependent potentiation in IL-1β- and PDBu-stimulated IL-8 release without affecting mRNA levels. Incubation with budesonide, fluticasone, and erythromycin caused dosedependent suppression of IL-1β- or PDBu-stimulated IL-8 release in the presence of pyocyanin. Budesonide and fluticasone were equally potent in the inhibition at 10 nM whilst erythromycin exerted its effect at a much higher dose at 30 µM. Our findings suggest that potentiation of IL-1β- or PDBu-induced IL-8 release by pyocyanin may be due to post-transcriptional mechanisms. These data confirm the established role of glucocorticosteroids, and erythromycin as anti-inflammatory action in treating bronchiectasis. Supported by Hong Kong RGC CERG (HKU 7353/03M).