title: Alteration of constitutive apoptosis in neutrophils by quinolones.
abstract: Neutrophils constitutively undergo apoptosis at sites of infection. The process of apoptosis controls inflammatory responses of neutrophils. However, little is known about the abilities of quinolones, which are often administered to patients showing infection disease, on constitutive apoptosis of neutrophils. The aim of this study is to evaluate abilities of quinolones on constitutive apoptosis of neutrophils. Tosufloxacin delayed neutrophil death and delayed neutrophil apoptosis. In contrast, ofloxacin, lomefloxacin, fleroxacin, sparfloxacin, and levofloxacin markedly promoted neutrophil death without affecting neutrophil apoptosis. Inhibitors of phosphoinositide 3-kinase (PI3K) and p38 mitogen-activated protein kinase (MAPK) attenuated the delay of neutrophil apoptosis by tosufloxacin, respectively. However, an inhibitor of extracellular-signal-related kinase did not alter the delay of neutrophil apoptosis by tosufloxacin. Moreover, tosufloxacin increases the expression of p85, p110beta, and Akt protein in neutrophils. These results suggest that tosufloxacin may delay neutrophil apoptosis via activation of PI3K/Akt and/or p38 MAPK, and the other quinolones may promote neutrophil death without affecting their apoptosis.
authors.affiliation: Department of Pharmacology, Osaka Dental University, Hirakata, Osaka, Japan. aazuma@cc.osaka-dent.ac.jp
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Azuma
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ohura
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004791:Enzyme Inhibitors; D015363:Quinolones