Effects of trovafloxacin on the IL-1-dependent activation of E-selectin inhuman endothelial cells in vitro

E-selectin is an endotholial-specific surface protein, which is transiently expressed in response to inflammatory cytokines and plays an important rol e in thr recruitment of leukocytes to the site of infection. The effect of two fluoroquinolones, ciprofloxacin (cipro) and trovafloxacin (trova), on t he interleukin-1 (IL-1)-dependent activation of E-Selectin was studied on h uman umbilical vein endothelial cells (HUVEC) in vitro. Trova, at 80 mu g/m l, affected the transient expression of E-selectin mRNA after pro-inflammat ory stimulation with IL-I leading to a sustained expression over 24 h. Surf ace expression of E-selectin remained upregulated after 24 h in a higher pe rcentage of cells when they were activated in the presence of trova, as det ermined by now cytometry analysis. Moreover, the concentration of shedded s oluble E-selectin (sE-selectin) in the cell supernatant increased by 3.5 fo ld compared to those stimulated in the presence of cipro or without fluoroq uinolones. Analogously, the antiproliferative effect of trova on endothelia l cells was found to be more pronounced compared to cipro leading to an acc umulation of cells arrested in G1-phase. These data provide evidence that a ccumulation of high concentration of trova in vivo in inflamed tissue might alter inflammatory responses. (C) 2000 Elsevier Science B.V. All rights re served.