title: Effects of trovafloxacin on the IL-1-dependent activation of E-selectin in human endothelial cells in vitro.
abstract: E-selectin is an endothelial-specific surface protein, which is transiently expressed in response to inflammatory cytokines and plays an important role in the recruitment of leukocytes to the site of infection. The effect of two fluoroquinolones, ciprofloxacin (cipro) and trovafloxacin (trova), on the interleukin-1 (IL-1)-dependent activation of E-Selectin was studied on human umbilical vein endothelial cells (HUVEC) in vitro. Trova, at 80 microg/ml, affected the transient expression of E-selectin mRNA after pro-inflammatory stimulation with IL-1 leading to a sustained expression over 24 h. Surface expression of E-selectin remained upregulated after 24 h in a higher percentage of cells when they were activated in the presence of trova, as determined by flow cytometry analysis. Moreover, the concentration of shedded soluble E-selectin (sE-selectin) in the cell supernatant increased by 3.5 fold compared to those stimulated in the presence of cipro or without fluoroquinolones. Analogously, the antiproliferative effect of trova on endothelial cells was found to be more pronounced compared to cipro leading to an accumulation of cells arrested in G1-phase. These data provide evidence that accumulation of high concentration of trova in vivo in inflamed tissue might alter inflammatory responses.
authors.affiliation: Department of Internal Medicine IV, University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria.
authors.forename: S M
authors.initials: SM
authors.lastname: Zakeri
authors.forename: H
authors.initials: H
authors.lastname: Meyer
authors.forename: G
authors.initials: G
authors.lastname: Meinhardt
authors.forename: W
authors.initials: W
authors.lastname: Reinisch
authors.forename: K
authors.initials: K
authors.lastname: Schrattbauer
authors.forename: M
authors.initials: M
authors.lastname: Knoefler
authors.forename: L H
authors.initials: LH
authors.lastname: Block
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002939:Ciprofloxacin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D024841:Fluoroquinolones; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D009287:Naphthyridines / Q000494:pharmacology*; D011419:Propidium; D012333:RNA, Messenger / Q000096:biosynthesis; D013997:Time Factors
chemical_list: D000890:Anti-Infective Agents; D019040:E-Selectin; D024841:Fluoroquinolones; D007375:Interleukin-1; D009287:Naphthyridines; D012333:RNA, Messenger; D011419:Propidium; D002939:Ciprofloxacin; C080163:trovafloxacin