Several gene programs are induced in ciprofloxacin-treated human lymphocytes as revealed by microarray analysis

Abstract: Fluoroquinolones have immunomodu-latory properties and interfere with cytokine pro-duction. The aim of this study was to characterize the extent of the superinduced mRNA levels in activated human lymphocytes incubated with cip-rofloxacin (5 and 80 g/ml) using a cytokine gene expression microarray from R&D Systems (Abing-don, UK). Several gene transcripts (n104) were up-regulated in cells treated with ciprofloxacin at 80 g/ml, whereas 98 transcripts were down-reg-ulated out of 847 total genes included on the mi-croarray. The increased mRNAs were distributed between major gene programs, including interleu-kins (36.5%), signal-transduction molecules (13.5%), adhesion molecules (10.6%), tumor ne-crosis factor and transforming growth factor- su-perfamilies (10.6%), cell-cycle regulators (9.6%), and apoptosis-related molecules (8.7%). To deter-mine the specificity of the microarray, a quantita-tive reverse transcriptase-polymerase chain reac-tion (RT-PCR), which contained a panel of 12 dif-ferent cytokine mRNAs, was used. Eleven out of the 12 gene transcripts were up-regulated in the specific RT-PCR, whereas only eight were found to be increased in the microarray. A microarray from Clontech (Hampshire, UK), containing 588 differ-ent genes, was also included. Results obtained with this broad-coverage expression array slightly dif-fered compared with the other microarray. We conclude that the fluoroquinolone ciprofloxacin at high concentrations interferes with several gene programs, which is in accordance with a mamma-lian stress response. From a technical point of view, a discrepancy may exist between data ob-tained by different microarrays and more specific methods such as quantitative RT-PCR. J. Leukoc